This document provides an overview of ion channels. It discusses how ion channels and transport proteins maintain homeostasis by regulating ion concentrations across membranes. It describes the key differences between channel and carrier proteins, noting that channels act like tunnels and carriers act like gates. The document outlines different types of ion channels including voltage-gated sodium channels, voltage-gated potassium channels, and voltage-gated calcium channels. It provides details on the structure and function of these channel proteins.
Non-coding RNAs (ncRNAs) are functional RNA molecules that are not translated into proteins. There are several types of ncRNAs that play important roles in biological processes. tRNAs help translate nucleotides into amino acids during protein synthesis. rRNA and snoRNAs are involved in ribosome and RNA structure/modification. MiRNAs regulate gene expression by binding to mRNA. LncRNAs regulate processes like chromatin structure and transcription. Mt-tRNAs specific to mitochondria are essential for oxidative phosphorylation. Mutations can cause diseases like myopathies.
microRNA/miRNA,Biochemistry-definition,who discovered it and how,types of miRNA,functions of microRNA,processing in nucleus and cytoplasm,applications,RISC
RNA serves various essential functions in biology. There are two main types: coding RNA (mRNA) which is translated into proteins, and non-coding RNA (ncRNA) which has regulatory functions but is not translated. Major ncRNAs include tRNA, which transports amino acids to the ribosome during protein synthesis, and rRNA, which along with proteins makes up the ribosome and catalyzes peptide bond formation. NcRNAs can regulate genes at the transcription or translation level. In eukaryotes, the majority of genomic transcripts are ncRNAs with diverse roles in splicing, translation, and gene expression control.
Viral vectors are efficient tools for gene delivery due to viruses' ability to transfer DNA into host cells. The document discusses several types of viral vectors, including adenoviral, adeno-associated, retroviral, lentiviral, and baculovirus vectors. It provides details on the structure and genome organization of different viruses used to create these vectors. The document also explains the process of generating recombinant viral vectors by removing unnecessary viral genes and inserting genes of interest. Viral vectors allow for transient or stable gene expression and are useful for both research and clinical applications such as gene therapy and vaccine development.
DNA Protein interaction occur when a protein binds a molecule of DNA, often to regulate the biological function of DNA, usually the expression of a gene. DNA Protein interactions play very vital roles in any living cell. It controls various cellular processes which are very essential for living beings, viz. replication, transcription, recombination, DNA repair etc. There are several types of proteins found in a cell.Direct recognition occurs when the amino acid side chains of a protein interact with specific DNA bases.
Most protein-DNA interactions are mediated by direct physical interaction (hydrogen bonding or hydrophobic interactions) between the protein and the DNA base pairs.
DNA-binding proteins can be identified by many experimental techniques such as chromatin immunoprecipitation on microarrays, X-ray crystallography and nuclear magnetic resonance (NMR).
RNA editing is a term associated with structural changes in an RNA strand that alter its coding properties. These enzyme-catalyzed reactions include nucleotide and oligonucleotide insertions and deletions as well as base modifications. The diversity of coding strands created by these reactions contributes to the protein diversity present in cells of higher organisms. In this review, we highlight advances in our understanding of the structure, mechanism, regulation, and biological functions of the ADAR enzymes published in the last five years. The ADARs (adenosine deaminases that act on RNA) are multidomain enzymes capable of converting adenosine to inosine at specific locations in certain RNA substrates. These reactions can change codon meaning in mRNA and lead to changes in the structures of proteins, including ligand-gated and voltage-gated ion channels and G-protein coupled receptors expressed in the central nervous system.
Major Histocompatibility complex & Antigen Presentation and ProcessingSreeraj Thamban
The document discusses the major histocompatibility complex (MHC) and antigen processing and presentation. It describes MHC molecules as polymorphic glycoproteins that play a role in discriminating self from non-self and participate in both humoral and cell-mediated immunity. MHC class I molecules present endogenous antigens on most nucleated cells and interact with CD8+ T cells. MHC class II molecules present exogenous antigens on antigen-presenting cells and interact with CD4+ T cells. Antigens are processed into peptides of appropriate size and bound motifs to be presented in the binding groove of MHC molecules.
The document discusses various topics related to enzymes, including:
1. The classification system for enzymes known as EC numbers which divides enzymes into six main groups based on reaction type.
2. Metal and vitamin cofactors that some enzymes require to function, such as iron, magnesium, flavin adenine dinucleotide, and niacin.
3. Factors that can affect an enzyme's activity, including temperature, pH, substrate and inhibitor concentration, and how activity varies with each factor.
Non-coding RNAs (ncRNAs) are functional RNA molecules that are not translated into proteins. There are several types of ncRNAs that play important roles in biological processes. tRNAs help translate nucleotides into amino acids during protein synthesis. rRNA and snoRNAs are involved in ribosome and RNA structure/modification. MiRNAs regulate gene expression by binding to mRNA. LncRNAs regulate processes like chromatin structure and transcription. Mt-tRNAs specific to mitochondria are essential for oxidative phosphorylation. Mutations can cause diseases like myopathies.
microRNA/miRNA,Biochemistry-definition,who discovered it and how,types of miRNA,functions of microRNA,processing in nucleus and cytoplasm,applications,RISC
RNA serves various essential functions in biology. There are two main types: coding RNA (mRNA) which is translated into proteins, and non-coding RNA (ncRNA) which has regulatory functions but is not translated. Major ncRNAs include tRNA, which transports amino acids to the ribosome during protein synthesis, and rRNA, which along with proteins makes up the ribosome and catalyzes peptide bond formation. NcRNAs can regulate genes at the transcription or translation level. In eukaryotes, the majority of genomic transcripts are ncRNAs with diverse roles in splicing, translation, and gene expression control.
Viral vectors are efficient tools for gene delivery due to viruses' ability to transfer DNA into host cells. The document discusses several types of viral vectors, including adenoviral, adeno-associated, retroviral, lentiviral, and baculovirus vectors. It provides details on the structure and genome organization of different viruses used to create these vectors. The document also explains the process of generating recombinant viral vectors by removing unnecessary viral genes and inserting genes of interest. Viral vectors allow for transient or stable gene expression and are useful for both research and clinical applications such as gene therapy and vaccine development.
DNA Protein interaction occur when a protein binds a molecule of DNA, often to regulate the biological function of DNA, usually the expression of a gene. DNA Protein interactions play very vital roles in any living cell. It controls various cellular processes which are very essential for living beings, viz. replication, transcription, recombination, DNA repair etc. There are several types of proteins found in a cell.Direct recognition occurs when the amino acid side chains of a protein interact with specific DNA bases.
Most protein-DNA interactions are mediated by direct physical interaction (hydrogen bonding or hydrophobic interactions) between the protein and the DNA base pairs.
DNA-binding proteins can be identified by many experimental techniques such as chromatin immunoprecipitation on microarrays, X-ray crystallography and nuclear magnetic resonance (NMR).
RNA editing is a term associated with structural changes in an RNA strand that alter its coding properties. These enzyme-catalyzed reactions include nucleotide and oligonucleotide insertions and deletions as well as base modifications. The diversity of coding strands created by these reactions contributes to the protein diversity present in cells of higher organisms. In this review, we highlight advances in our understanding of the structure, mechanism, regulation, and biological functions of the ADAR enzymes published in the last five years. The ADARs (adenosine deaminases that act on RNA) are multidomain enzymes capable of converting adenosine to inosine at specific locations in certain RNA substrates. These reactions can change codon meaning in mRNA and lead to changes in the structures of proteins, including ligand-gated and voltage-gated ion channels and G-protein coupled receptors expressed in the central nervous system.
Major Histocompatibility complex & Antigen Presentation and ProcessingSreeraj Thamban
The document discusses the major histocompatibility complex (MHC) and antigen processing and presentation. It describes MHC molecules as polymorphic glycoproteins that play a role in discriminating self from non-self and participate in both humoral and cell-mediated immunity. MHC class I molecules present endogenous antigens on most nucleated cells and interact with CD8+ T cells. MHC class II molecules present exogenous antigens on antigen-presenting cells and interact with CD4+ T cells. Antigens are processed into peptides of appropriate size and bound motifs to be presented in the binding groove of MHC molecules.
The document discusses various topics related to enzymes, including:
1. The classification system for enzymes known as EC numbers which divides enzymes into six main groups based on reaction type.
2. Metal and vitamin cofactors that some enzymes require to function, such as iron, magnesium, flavin adenine dinucleotide, and niacin.
3. Factors that can affect an enzyme's activity, including temperature, pH, substrate and inhibitor concentration, and how activity varies with each factor.
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
Microbial fuel cells are newest technological advancement in conventional fuel cell technology. Treatment of wastewater is coupled with electricity generation. Hydrogen production is also possible by modifying MFC technology. It is a independent essential review of Microbial fuel cell technology.
detail description about different models of DNA helicase. basically 2 types of mechanism involved in the helicase function and it has various models. this information is refer from research paper and some review articles.
B-cell maturation begins with hematopoietic stem cells in the bone marrow, where they develop through pro-B cell, pre-B cell, and immature B cell stages. During this process, immunoglobulin genes undergo rearrangement and expression of B cell receptors occurs. Immature B cells then migrate to secondary lymphoid tissues to complete maturation. Mature B cells circulate and are activated by antigen to proliferate and differentiate into plasma cells or memory B cells through T cell dependent or independent pathways. T cell dependent activation induces affinity maturation, class switching, and generation of long-lived memory B cells.
This document discusses metabolic pathway analysis. It defines metabolic pathways as series of consecutive enzyme reactions that produce specific products. It notes that pathways are irreversible and compartmentalization allows different cycles to operate in eukaryotes. The document outlines several methods to analyze pathways, including isotope labeling, genome-scale metabolic modeling, and structural kinetic modeling. It provides the example of glycolysis and describes applications like finding high yield pathways and determining active reactions.
RNA is a polymer made of ribonucleotides linked together. There are three main classes of RNA - transfer RNA, ribosomal RNA, and messenger RNA. In eukaryotes, primary transcripts undergo processing including capping, polyadenylation, and splicing before being transported to the cytoplasm for translation. MicroRNAs and small interfering RNAs are types of small regulatory RNAs that cause inhibition of gene expression through post-transcriptional gene silencing. Both miRNAs and siRNAs have potential applications as therapeutic targets in humans.
This document summarizes different types of DNA repair mechanisms including base excision repair, nucleotide excision repair, and their mechanisms in E. coli and humans. It also discusses short patch and long patch base excision repair, and conditions like xeroderma pigmentosum that arise from defects in nucleotide excision repair.
Thymidine kinase (TK), dihydrofolate reductase (dhfr), and chloramphenicol acetyl transferase (CAT) are examples of selectable marker genes used for animal cells. Marker genes help monitor transfection by allowing detection of whether the transgene was successfully transferred. Selectable marker genes enable transformed cells to survive selection conditions that kill non-transformed cells.
RNA interference (RNAi) is a mechanism where double-stranded RNA inhibits gene expression. It was discovered in plants, fungi, and animals. The mechanism involves dicer enzymes cleaving long double-stranded RNA into short interfering RNAs (siRNAs). These siRNAs are incorporated into an RNA-induced silencing complex (RISC) which guides the complex to mRNAs with complementary sequences, resulting in their degradation. RNAi has applications in therapeutics for cancer, viruses, and genetic disorders, as well as research in gene function and pathways.
This document provides an overview of microcarrier cell culture principles and methods. Microcarriers allow for increased surface area for cell attachment and growth compared to traditional cell culture methods. They enable higher cell densities and product yields by separating cells from culture medium, improving process control and scalability. Various microcarrier types made from different materials are available for culturing different cell types like mammalian, insect and plant cells. Microcarriers are used to produce vaccines, proteins, antibodies and more in small-scale equipment like spinners and roller bottles as well as large-scale bioreactors like stirred tanks, packed beds and fluidized beds. Careful selection of microcarrier properties, culture conditions and control strategies are required to optimize microcarrier cell culture
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
The process of transcription is the first stage of gene expression resulting in the production of a primary RNA transcript from the DNA of a particular gene.
This step of gene expression which is followed by a number of post-transcriptional processes such as RNA splicing and translation.
These lead ultimately to the production of a functional protein and this process is highly regulated.
Both basal transcription and its regulation are dependent upon specific protein factors known as transcription factors.
These highly specific protein bind to the specific regulatory gene of DNA sequence and control the transcription process and regulate it.
For example- enzyme RNA polymerase catalyzes the chemical reaction that synthesize RNA, using the DNA gene as a template, the transcription factor control when, where, and how efficiency RNA polymerase function.
Play an important role in the normal development and routine of cellular function.
Zinc finger nucleases (ZFNs) allow for highly targeted editing of the genome. ZFNs consist of a DNA-binding domain made of zinc finger proteins and a DNA-cleaving domain. The ZFN pair binds to a target site and creates a double-strand break, which the cell repairs through non-homologous end joining or homologous recombination, enabling gene knockouts or targeted changes. ZFNs work in many cell types and animal models, providing a more efficient alternative to traditional transgenic techniques. They have applications in functional genomics, cell line engineering, and animal model generation.
E. coli RNA polymerase is an enzyme that catalyzes the formation of phosphodiester bonds between nucleotides during transcription. It is composed of five subunits - two α subunits, one β subunit, one β' subunit, and one ω subunit. Together with a sigma factor, these subunits form the holoenzyme which is required for transcription initiation by binding to promoter sequences on DNA. The sigma factor recognizes specific promoter sequences and directs the holoenzyme to begin RNA synthesis. E. coli has multiple sigma factors that direct transcription of different genes depending on environmental conditions.
The document discusses protein-DNA interactions and binding mechanisms. It covers several key points:
1) Specific binding of proteins to nucleic acids underlies gene expression processes like replication, repair, transcription and RNA metabolism.
2) Mechanisms of protein-DNA binding include the release of water molecules and ions, allowing the structures to conform and form hydrogen bonds and electrostatic interactions.
3) Recognition principles involve interactions with bases in the major/minor grooves, with certain amino acids preferring certain bases. Sequence-specific binding involves shape complementarity and electrostatic patches on the proteins.
Gene expression in prokaryotes involves the process of genetic information from DNA being made into functional gene products like proteins or RNA. Prokaryotes lack nuclei but have efficient genetic mechanisms to respond to the environment. They regulate gene expression through inducible and constitutive genes in response to substrates. A key example is the lac operon model in E. coli, which regulates 3 genes for lactose breakdown in response to lactose or IPTG through transcription control by a repressor protein.
This document provides an overview of non-coding RNA (ncRNA), including long ncRNAs and small ncRNAs. It discusses different types of small ncRNAs such as microRNAs (miRNAs), piRNAs, and small interfering RNAs (siRNAs). The document describes the biogenesis and mechanisms of action of these ncRNAs. It provides examples of functions for long ncRNAs and the role of the siRNA pathway in preventing transgenerational retrotransposition in plants under stress. In summary, the document categorizes and explains the major types and roles of coding and non-coding RNAs.
The ubiquitin-proteasome system (UPS) is a mechanism for intracellular protein degradation that involves tagging proteins with ubiquitin and recognizing them using the 26S proteasome. The 26S proteasome contains a 20S core particle for protein degradation and two 19S regulatory particles. Target proteins are tagged with ubiquitin by enzymes (E1, E2, E3) and recognized by the 19S particle. They are unfolded and fed into the 20S core where three catalytic subunits (β1, β2, β5) degrade the proteins into small peptides. The UPS plays important roles in various cellular processes and was discovered by scientists Ciechanover, Hershko, and Rose,
Ion channels are pore-forming membrane proteins that regulate the flow of ions across cell membranes. There are several types of ion channels classified by their gating mechanism and selectivity for specific ions like potassium, sodium, calcium, and chloride. Voltage-gated ion channels open or close in response to changes in membrane potential, while ligand-gated channels are activated by binding of neurotransmitters or other ligands. Ion channels play crucial roles in generating electrical signals in excitable cells and regulating various cellular processes. Diseases caused by mutations in ion channel genes are known as channelopathies.
Ion channel gating in plants is regulated by various factors including ligands, membrane potential, stretch, and light. There are four main types of ion channels: ligand-gated, voltage-gated, stretch-activated, and light-activated. Voltage-gated ion channels are composed of alpha and beta subunits and contain voltage sensor domains that undergo conformational changes in response to changes in membrane potential. Ligand-gated channels open when ligands like neurotransmitters bind to the channel. Precise control of ion channel gating is essential for physiological functioning of plant cells.
B cell generation-activation_and_differentiationDUSHYANT KUMAR
B cells develop through several stages:
1) Generation in the bone marrow or fetal liver
2) Activation in the lymph nodes through interaction with antigens and T cells
3) Differentiation into plasma cells, which secrete antibodies, or memory B cells
The key events in B cell activation and differentiation are Ig gene rearrangement, affinity maturation through somatic hypermutation, class switch recombination, and formation of plasma cells and memory cells mediated by AID and specific cytokines in germinal centers. B cells can be activated through T cell dependent or independent pathways.
Microbial fuel cells are newest technological advancement in conventional fuel cell technology. Treatment of wastewater is coupled with electricity generation. Hydrogen production is also possible by modifying MFC technology. It is a independent essential review of Microbial fuel cell technology.
detail description about different models of DNA helicase. basically 2 types of mechanism involved in the helicase function and it has various models. this information is refer from research paper and some review articles.
B-cell maturation begins with hematopoietic stem cells in the bone marrow, where they develop through pro-B cell, pre-B cell, and immature B cell stages. During this process, immunoglobulin genes undergo rearrangement and expression of B cell receptors occurs. Immature B cells then migrate to secondary lymphoid tissues to complete maturation. Mature B cells circulate and are activated by antigen to proliferate and differentiate into plasma cells or memory B cells through T cell dependent or independent pathways. T cell dependent activation induces affinity maturation, class switching, and generation of long-lived memory B cells.
This document discusses metabolic pathway analysis. It defines metabolic pathways as series of consecutive enzyme reactions that produce specific products. It notes that pathways are irreversible and compartmentalization allows different cycles to operate in eukaryotes. The document outlines several methods to analyze pathways, including isotope labeling, genome-scale metabolic modeling, and structural kinetic modeling. It provides the example of glycolysis and describes applications like finding high yield pathways and determining active reactions.
RNA is a polymer made of ribonucleotides linked together. There are three main classes of RNA - transfer RNA, ribosomal RNA, and messenger RNA. In eukaryotes, primary transcripts undergo processing including capping, polyadenylation, and splicing before being transported to the cytoplasm for translation. MicroRNAs and small interfering RNAs are types of small regulatory RNAs that cause inhibition of gene expression through post-transcriptional gene silencing. Both miRNAs and siRNAs have potential applications as therapeutic targets in humans.
This document summarizes different types of DNA repair mechanisms including base excision repair, nucleotide excision repair, and their mechanisms in E. coli and humans. It also discusses short patch and long patch base excision repair, and conditions like xeroderma pigmentosum that arise from defects in nucleotide excision repair.
Thymidine kinase (TK), dihydrofolate reductase (dhfr), and chloramphenicol acetyl transferase (CAT) are examples of selectable marker genes used for animal cells. Marker genes help monitor transfection by allowing detection of whether the transgene was successfully transferred. Selectable marker genes enable transformed cells to survive selection conditions that kill non-transformed cells.
RNA interference (RNAi) is a mechanism where double-stranded RNA inhibits gene expression. It was discovered in plants, fungi, and animals. The mechanism involves dicer enzymes cleaving long double-stranded RNA into short interfering RNAs (siRNAs). These siRNAs are incorporated into an RNA-induced silencing complex (RISC) which guides the complex to mRNAs with complementary sequences, resulting in their degradation. RNAi has applications in therapeutics for cancer, viruses, and genetic disorders, as well as research in gene function and pathways.
This document provides an overview of microcarrier cell culture principles and methods. Microcarriers allow for increased surface area for cell attachment and growth compared to traditional cell culture methods. They enable higher cell densities and product yields by separating cells from culture medium, improving process control and scalability. Various microcarrier types made from different materials are available for culturing different cell types like mammalian, insect and plant cells. Microcarriers are used to produce vaccines, proteins, antibodies and more in small-scale equipment like spinners and roller bottles as well as large-scale bioreactors like stirred tanks, packed beds and fluidized beds. Careful selection of microcarrier properties, culture conditions and control strategies are required to optimize microcarrier cell culture
Mismatch Repair Mechanism Is One Of The Important DNA Repair Mechanism Which Recognizes And Replaces The Wrong Nucleotides. DNA Repair Is Important Since Its Failure Leads To Deadly Diseases Like Cancer. In This Presentation, You Will Learn About DNA Repair, Mismatch Repair, Proteins Involved In Prokaryotic And Eukaryotic MMR, Diagrams, Biological Importance Of MMR And References For Further Study.
The process of transcription is the first stage of gene expression resulting in the production of a primary RNA transcript from the DNA of a particular gene.
This step of gene expression which is followed by a number of post-transcriptional processes such as RNA splicing and translation.
These lead ultimately to the production of a functional protein and this process is highly regulated.
Both basal transcription and its regulation are dependent upon specific protein factors known as transcription factors.
These highly specific protein bind to the specific regulatory gene of DNA sequence and control the transcription process and regulate it.
For example- enzyme RNA polymerase catalyzes the chemical reaction that synthesize RNA, using the DNA gene as a template, the transcription factor control when, where, and how efficiency RNA polymerase function.
Play an important role in the normal development and routine of cellular function.
Zinc finger nucleases (ZFNs) allow for highly targeted editing of the genome. ZFNs consist of a DNA-binding domain made of zinc finger proteins and a DNA-cleaving domain. The ZFN pair binds to a target site and creates a double-strand break, which the cell repairs through non-homologous end joining or homologous recombination, enabling gene knockouts or targeted changes. ZFNs work in many cell types and animal models, providing a more efficient alternative to traditional transgenic techniques. They have applications in functional genomics, cell line engineering, and animal model generation.
E. coli RNA polymerase is an enzyme that catalyzes the formation of phosphodiester bonds between nucleotides during transcription. It is composed of five subunits - two α subunits, one β subunit, one β' subunit, and one ω subunit. Together with a sigma factor, these subunits form the holoenzyme which is required for transcription initiation by binding to promoter sequences on DNA. The sigma factor recognizes specific promoter sequences and directs the holoenzyme to begin RNA synthesis. E. coli has multiple sigma factors that direct transcription of different genes depending on environmental conditions.
The document discusses protein-DNA interactions and binding mechanisms. It covers several key points:
1) Specific binding of proteins to nucleic acids underlies gene expression processes like replication, repair, transcription and RNA metabolism.
2) Mechanisms of protein-DNA binding include the release of water molecules and ions, allowing the structures to conform and form hydrogen bonds and electrostatic interactions.
3) Recognition principles involve interactions with bases in the major/minor grooves, with certain amino acids preferring certain bases. Sequence-specific binding involves shape complementarity and electrostatic patches on the proteins.
Gene expression in prokaryotes involves the process of genetic information from DNA being made into functional gene products like proteins or RNA. Prokaryotes lack nuclei but have efficient genetic mechanisms to respond to the environment. They regulate gene expression through inducible and constitutive genes in response to substrates. A key example is the lac operon model in E. coli, which regulates 3 genes for lactose breakdown in response to lactose or IPTG through transcription control by a repressor protein.
This document provides an overview of non-coding RNA (ncRNA), including long ncRNAs and small ncRNAs. It discusses different types of small ncRNAs such as microRNAs (miRNAs), piRNAs, and small interfering RNAs (siRNAs). The document describes the biogenesis and mechanisms of action of these ncRNAs. It provides examples of functions for long ncRNAs and the role of the siRNA pathway in preventing transgenerational retrotransposition in plants under stress. In summary, the document categorizes and explains the major types and roles of coding and non-coding RNAs.
The ubiquitin-proteasome system (UPS) is a mechanism for intracellular protein degradation that involves tagging proteins with ubiquitin and recognizing them using the 26S proteasome. The 26S proteasome contains a 20S core particle for protein degradation and two 19S regulatory particles. Target proteins are tagged with ubiquitin by enzymes (E1, E2, E3) and recognized by the 19S particle. They are unfolded and fed into the 20S core where three catalytic subunits (β1, β2, β5) degrade the proteins into small peptides. The UPS plays important roles in various cellular processes and was discovered by scientists Ciechanover, Hershko, and Rose,
Ion channels are pore-forming membrane proteins that regulate the flow of ions across cell membranes. There are several types of ion channels classified by their gating mechanism and selectivity for specific ions like potassium, sodium, calcium, and chloride. Voltage-gated ion channels open or close in response to changes in membrane potential, while ligand-gated channels are activated by binding of neurotransmitters or other ligands. Ion channels play crucial roles in generating electrical signals in excitable cells and regulating various cellular processes. Diseases caused by mutations in ion channel genes are known as channelopathies.
Ion channel gating in plants is regulated by various factors including ligands, membrane potential, stretch, and light. There are four main types of ion channels: ligand-gated, voltage-gated, stretch-activated, and light-activated. Voltage-gated ion channels are composed of alpha and beta subunits and contain voltage sensor domains that undergo conformational changes in response to changes in membrane potential. Ligand-gated channels open when ligands like neurotransmitters bind to the channel. Precise control of ion channel gating is essential for physiological functioning of plant cells.
This document provides an overview of ion channels and transporters. It discusses that ion channels are integral membrane proteins that form pores to allow passive transport of ions across cell membranes. Ion channels can be voltage-gated, opening and closing in response to changes in membrane voltage, or ligand-gated, opening when neurotransmitters or other ligands bind. The document also describes different types of ion channels, including sodium, potassium, calcium, and anion channels. Additionally, it discusses ion transporters like uniporters and antiporters that actively transport ions against gradients using ATP.
plasmodesmata, porins, ion channels, membrane potentialCherry
Membranes define intracellular organelles and separate intracellular and extracellular environments. Biological membranes have a similar basic architecture consisting of a phospholipid bilayer with embedded proteins. Plasmodesmata are cytoplasmic channels between plant cells that allow communication and transport of molecules. They have a plasma membrane, desmotubule, and cytoplasmic sleeve. Ion channels are membrane proteins that selectively transport ions according to membrane potential or ligand binding. Voltage-gated potassium channels open and close in response to changes in membrane potential via movement of voltage-sensing domains.
ion channel and carrier protein By KK Sahu SirKAUSHAL SAHU
INTRODUCTION - DEFINITION OF ION CANALS- HISTORY AND DIVERSITY OF ION CANALS- CARRIER PROTEIN-DEFINITION - CLASSES OF CARRIER PROTEIN - MECHANISM OF ION CANALS AND CARRIER PROTEIN - MEMBRANE TRANSPORT- BIOLOGICAL ROLE OF ION CANALS AND CARRIER PROTEIN - CONCLUSION - REFERENCE
Ion channels, types and their importace in managment of diseasesFarazaJaved
This topic covers voltage gated type of ion channel, general structure and functioning of ion channels and involvement of different ion channel types in the pathogenesis as wella as a target for the development of various diseases.
This document summarizes key aspects of cell membrane structure and function:
- The cell membrane consists of a lipid bilayer with embedded protein molecules that transport substances across. Channel proteins allow passage of specific molecules, while carrier proteins bind and transport selected molecules or ions.
- Transport across the membrane occurs through passive diffusion or active transport. Passive transport includes simple diffusion of lipid-soluble substances through the bilayer and facilitated diffusion using carrier proteins. Active transport requires energy to move substances against a concentration gradient.
- Protein channels can be selectively permeable and gated to open and close based on electrical or chemical signals, precisely regulating transport. Factors like concentration gradients, electrical potential, and pressure differentials determine the
Potassium channels are widely distributed ion channels that regulate cell functions by conducting potassium ions across cell membranes. They have a tetrameric structure and a selectivity filter that selectively allows potassium ions to pass through. Potassium channels are regulated by gating and inactivation and come in several types including calcium-activated, inward rectifying, tandem pore domain, and voltage-gated channels. Dysfunctions in potassium channels can lead to diseases.
This document discusses transport across cell membranes. It explains that cells use facilitated diffusion and active transport to move molecules and ions across membranes. Facilitated diffusion uses protein channels and transporters to help molecules and ions diffuse down their concentration gradients. Active transport uses transmembrane proteins called pumps that directly harness ATP energy to transport molecules against their gradients. Key examples of pumps discussed are the Na+/K+ ATPase in animal cells and H+/K+ ATPase in stomach parietal cells.
The document summarizes key concepts about solute transport across membranes in plant and animal cells. It discusses passive diffusion of small molecules, facilitated diffusion mediated by carrier and channel proteins, and active transport driven by ATP hydrolysis including sodium-potassium pumps and co-transport. It also describes bulk transport mechanisms like phagocytosis, pinocytosis, and receptor-mediated endocytosis as well as exocytosis for exporting materials. The seminar was presented to discuss these transport mechanisms in detail.
Mechanism of transport of small molecules across membrane.pptxBharathReddy443625
This document discusses mechanisms of transporting small molecules across cell membranes. It begins by explaining that while some molecules like oxygen and carbon dioxide can diffuse through lipid bilayers, charged and polar molecules require transport mechanisms. It then describes three main types of transport - passive transport down concentration gradients or electrochemical gradients, active transport using transporter proteins and ion pumps, and transport through ion channels. Specific examples are given of aquaporin water channels, glucose and sodium symporters, calcium and sodium pumps, and different gated ion channels. The role of the sodium-potassium pump and potassium leak channels in generating the resting membrane potential is also explained.
1. The document describes the structure and functions of a typical animal cell. It discusses the discovery of cells and outlines the components of cells, including the cell membrane, nucleus, and cytoplasm.
2. The cell membrane is made of lipids and proteins and acts as a selective barrier for the cell. Transport across the membrane can occur through passive diffusion, facilitated diffusion, or active transport powered by the cell.
3. The key components of cells are the cell membrane, nucleus, and cytoplasm. Cells are the basic structural and functional units that make up living organisms.
Ion channels are membrane proteins that allow ions to pass through their pore, regulating ion flow and electrical signals. There are two main types of gated ion channels: ligand-gated channels, which open when neurotransmitters bind, and voltage-gated channels, which open in response to changes in membrane potential. Ligand-gated channels allow sodium influx upon acetylcholine binding, depolarizing the membrane and triggering action potentials. Voltage-gated channels maintain the resting potential and enable action potential propagation along axons by selectively transporting sodium, potassium, calcium, and chloride ions in response to changes in voltage.
This document discusses various mechanisms of transport across cell membranes, including:
1) Passive transport mechanisms like diffusion and facilitated diffusion of small molecules.
2) Active transport of ions and macromolecules against a concentration gradient using ATP.
3) Endocytosis and exocytosis for transport of large molecules and macromolecules across the membrane.
4) Specific transport proteins and ion channels that facilitate movement of substances in and out of cells.
Transmembrane transport of ions and small molecules by Kainat RamzanKainatRamzan3
The plasma membrane is a selectively permeable barrier between the cell and the extracellular environment. Its permeability properties ensure that essential molecules such as ions, glucose, amino acids, and lipids readily enter the cell, and waste compounds leave the cell.
Physiology at a glance 2013 keyrevisionpointsElsa von Licy
Homeostasis involves physiological systems maintaining equilibrium. The shape and binding of proteins is essential for their normal functioning and is maintained by homeostatic mechanisms. Small changes in the environment can modify protein shape. Negative feedback loops involving detectors, comparators and effectors regulate most physiological variables. [END SUMMARY]
The document discusses various aspects of membrane transport in cells. It explains that the plasma membrane defines cell borders and is selectively permeable, allowing some materials to pass through freely while others require transport proteins. It describes the fluid mosaic model of the plasma membrane and its components. Various modes of transport are summarized, including passive diffusion and facilitated diffusion, as well as active transport mechanisms like pumps, channels, and endocytosis/exocytosis. Nerve impulse transmission is also covered, explaining the resting membrane potential and how action potentials propagate signals in neurons.
cell membrane transport mechanisms and related disorders ppt..pptxNitinchaudharY351367
The document discusses cell membranes and transport mechanisms. It begins by describing the structure and function of the cell membrane, including that it is a lipid bilayer containing proteins. It then explains the different types of transport across membranes, including passive transport mechanisms like simple diffusion and facilitated diffusion, as well as active transport mechanisms like primary active transport using ATP and secondary active transport using ion gradients. Specific transport proteins and mechanisms discussed include sodium-potassium pumps, calcium pumps, hydrogen-potassium pumps, and sodium-glucose co-transporters. The document concludes by mentioning some applied aspects regarding transport mechanisms.
The plasma membrane is selectively permeable due to its structure of phospholipids and proteins. It contains transport proteins that selectively move molecules into and out of the cell, including ion channels, carriers, and pumps. Ion channels come in many varieties but generally involve selective permeability to ions and gating mechanisms. Transport proteins also include carriers that move molecules via symport, antiport, or uniport mechanisms, as well as ATP-dependent pumps and ABC transporters that use ATP to actively transport substances against gradients. Regulation of transport involves controlling expression and gating of specific transport proteins.
Lecture 4 (transport of substances through plasmallema)Ayub Abdi
The document summarizes the key mechanisms of transport across the cell membrane. It describes how lipid-soluble substances can diffuse directly through the lipid bilayer, while water and other molecules require protein channels. Transport occurs via diffusion, either simple diffusion through openings or facilitated diffusion using carrier proteins, or active transport against gradients using ATP or the sodium-potassium gradient. Protein channels provide selective permeability and can be gated to control transport.
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
Or: Beyond linear.
Abstract: Equivariant neural networks are neural networks that incorporate symmetries. The nonlinear activation functions in these networks result in interesting nonlinear equivariant maps between simple representations, and motivate the key player of this talk: piecewise linear representation theory.
Disclaimer: No one is perfect, so please mind that there might be mistakes and typos.
dtubbenhauer@gmail.com
Corrected slides: dtubbenhauer.com/talks.html
Travis Hills' Endeavors in Minnesota: Fostering Environmental and Economic Pr...Travis Hills MN
Travis Hills of Minnesota developed a method to convert waste into high-value dry fertilizer, significantly enriching soil quality. By providing farmers with a valuable resource derived from waste, Travis Hills helps enhance farm profitability while promoting environmental stewardship. Travis Hills' sustainable practices lead to cost savings and increased revenue for farmers by improving resource efficiency and reducing waste.
When I was asked to give a companion lecture in support of ‘The Philosophy of Science’ (https://shorturl.at/4pUXz) I decided not to walk through the detail of the many methodologies in order of use. Instead, I chose to employ a long standing, and ongoing, scientific development as an exemplar. And so, I chose the ever evolving story of Thermodynamics as a scientific investigation at its best.
Conducted over a period of >200 years, Thermodynamics R&D, and application, benefitted from the highest levels of professionalism, collaboration, and technical thoroughness. New layers of application, methodology, and practice were made possible by the progressive advance of technology. In turn, this has seen measurement and modelling accuracy continually improved at a micro and macro level.
Perhaps most importantly, Thermodynamics rapidly became a primary tool in the advance of applied science/engineering/technology, spanning micro-tech, to aerospace and cosmology. I can think of no better a story to illustrate the breadth of scientific methodologies and applications at their best.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
2. Introduction
Biological membranes - highly selective, permeable barriers that surround
distinct cellular compartments.
The plasma membrane separates the inside of the cell from the extracellular
environment, and within eukaryotic cells, additional membranes separate
specialized compartments from the cytosol.
Cellular compartments differ markedly in the composition of their membranes
and internal environment.
Throughout evolution, cells have developed sophisticated mechanisms to
precisely maintain and regulate the composition of each compartment.
3. Continued
The maintenance of solute concentrations across membranes is a prerequisite
for cellular homeostasis.
Homeostasis is the ability of cells to maintain a relatively constant internal
environment for metabolic processes that are vital for survival.
The homeostatic regulation of cytosolic ion concentrations also determines
the relative osmotic pressures on each side of the cell membrane and thereby
regulates the cell volume.
4. Mediated and non-mediated transport
Mediated transport
Through the action of
various carriers
Non-mediated
transport
Occurs through simple
diffusion; chemical
potential gradient is
the driving force
Transport processes
5.
6. Transport across membranes
Because the interior of the lipid bilayer is hydrophobic, it is essentially
impermeable to polar, hydrophilic and large biological molecules.
How do inorganic ions and charged and water-soluble molecules move into
and out of cells and across intracellular membranes in a selective manner?
Transport proteins reside in the plasma membrane and in membranes of
intracellular organelles such as endoplasmic reticulum(ER), golgi apparatus,
endosomes, lysosomes, and mitochondria
transport proteins are integral transmembrane proteins
Each type of membrane has distinct complement of transport proteins, as do
different cell types.
There are two main classes of transport proteins, channel proteins and carrier
proteins
7. Transport channels
Channels and Carriers are the main types of membrane transport proteins
Confer permeability to the membrane
Allosteric proteins
Some transport proteins are present in the plasma membrane, whereas others
are present in the membranes of intracellular organelles
To maintain the composition of the cell and its intracellular compartments, it
is important that transport are selective for a particular solute species over
other.
8.
9. Channels vs carriers
Membrane transport proteins can be classified into two groups, channels and
carriers, depending on the mode of transport.
Channels, composed of one or more subunits, contain a pore region through
which solute pass at high flux rates when the channel is open(acts like a
tunnel)
In contrast, carrier proteins bind solutes on one side of the membrane,
undergo an allosteric(conformational) change, and release the solutes on the
other side of the membrane(acts like a gate/door)
10. Properties of channels
Constructed by the association of multiple homologous subunits or domains .
Most channels are formed from four, five, six subunits
The pore lies along the symmetry axis of the channel
The pore is lined by α helices or β strands. Side chains emerging from these
structural elements establish the selectivity of the channel. The acetylcholine
receptor channel, for example, is selective for cations because its pore
contains negatively charged rings.
The degree of selectivity also depends on the diameter of the narrowest part
of the pore. Channels formed from four subunit (the Na and the K channel)
have the smallest pores(diameter 5Å and 3Å respectively) and are the most
selective
Channels are allosteric proteins that are gated by membrane potential ,
allosteric effectors, or covalent modification.
11. Transport channels: mode of operation
Ungated channels
A few types of channels are ungated, meaning they are open all the time.
For instance, some K+ and some Cl– channels are ungated. By contrast, Ca2+
and Na+ ion channels are never ungated.
Voltage gated channel
This require a trigger, such as a change in membrane potential to unlock or
lock the pore opening
Voltage-gated ion channels are key in the generation of electrical signals in
nerve, muscle, and cardiac cells.
12. Continued..
Ligand-gated channel
Many ion channels open or close in response to binding a small signaling molecule or “ligand”. Some
ion channels are gated by extracellular ligands; some by intracellular ligands.
In both cases, the ligand is not the substance that is transported when the channel opens. Many
neurotransmitter receptors are ligand gated channels.
An example is the nicotinic acetylcholine receptor. This is the receptor that is found at the
neuromuscular junction on skeletal muscle cells, and also at synapses in autonomic ganglia.
Stress-gated channel
This require a mechanical force applied to the channel for opening. Mechanically-gated channels are
found in skin and also in the specialized sensory cells of the auditory and vestibular system.
15. Ion channels
Ion channels are pore-forming membrane proteins
Located within the plasma membrane of nearly all cells and many
intracellular organelles
They are often described as narrow, water- filled tunnels that allow only ions
of certain size and/or charge to pass through. This characteristic is called
selective permeability
16.
17. Functions
Maintain cell resting potential: K and Cl channels
Conduction of electrical signals: Na and K channels of nerve axon
Synaptic transmission at nerve terminals
Intracellular transfer of ions, metabolites
Cell volume regulation: Cl channels
Excitation-contraction coupling: Ca channels of skeletal and heart muscle
18. Voltage gated channels
Voltage-gated ion channels - class of transmembrane proteins - form ion channels that are
activated by changes in the electrical membrane potential near the channel
The membrane potential alters the conformation of the channel proteins, regulating their opening
and closing
Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane
through transmembrane protein channels.
They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and
coordinated depolarization in response to triggering voltage change
Found along the axon and at the synapse, voltage-gated ion channels directionally propagate
electrical signals
Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+),
potassium (K+), calcium (Ca2+), and chloride (Cl–) ions have been identified.
19.
20. mechanism
Crystallographic structural studies of a potassium channel have shown that,
when a potential difference is introduced over the membrane, the associated
electric field induces a conformational change in the potassium channel
The conformational change distorts the shape of the channel proteins
sufficiently such that the cavity, or channel, opens to allow influx or efflux to
occur across the membrane
This movement of ions down their concentration gradients subsequently
generates an electric current sufficient to depolarize the cell membrane.
21. Types of voltage gated ion channels
1. Voltage gated sodium channels
2. Voltage gated potassium channels
3. Voltage gated calcium channels
4. Voltage gated chloride channels
22.
23. Voltage gated sodium channels
Analysis of the sodium channel function occurred in 1960’s, and in 1980, the voltage gated sodium
channel was discovered
essential in the nervous system and for the generation of action potentials in excitable cells,
including nerve, muscle and neuroendocrine cell types
Low levels in non-excitable cells- physiological role unclear
structure is similar to that of most other voltage gated ion channels; subunits arranged in such a
way so that a central pore is formed
the first voltage gated ion channel to be cloned and sequenced
Belongs to the superfamily of ion channels(first to be discovered)
24. Structure of voltage gated sodium
channel
consist of a highly processed α subunit, which is approximately 260 kDa, associated with auxiliary β subunits of 33-39 kDa [5].
Sodium channels in the adult central nervous system (CNS) and heart contain a mixture of β1 - β4 subunits, while sodium channels in adult skeletal
muscle have only the β1 subunit.
The pore-forming α subunit is sufficient for functional expression, but the kinetics and voltage-dependence of channel gating are modified by the β
subunits and these auxiliary subunits are involved in channel localization and interaction with cell adhesion molecules, extracellular matrix and
intracellular cytoskeleton.
The α subunits are organized in four homologous domains (I–IV), which each contain six transmembrane alpha helices (S1–S6) and an additional pore
loop located between the S5 and S6 segments
The pore loops line the outer entry to the pore while the S5 and S6 segments line the inner cavity and form activation gate at the inner exit from the
pore. The S4 segments in each domain contain positively charged amino acid residues (usually arginine) at every third position.
These residues serve as gating charges and move across the membrane in order to initiate channel activation in response to depolarization.
The short intracellular loop connecting homologous domains III and IV serves as the inactivation gate, folding into the channel structure and blocking
the pore from the inside during sustained depolarization of the membrane.
25.
26. Voltage gated potassium channels
Potassium channels are membrane proteins that allow rapid and selective
flow of 𝐾+ ions across the cell membrane, and thus generate electric signals
in cells
Voltage-gated 𝐾+
channels- present in all animal cells
Kv channels are one of the key components in generation and propagation of
electrical impulses in nervous system
The opening and closing of the channel depends upon changes in the
transmembrane potential
Upon changes in transmembrane potential, these channels open and allow
passive flow of 𝐾+
ions from the cell to restore the membrane potential
27.
28. Voltage gated calcium channels
Voltage gated calcium(𝐶𝑎2+
) channels are key transducers of membrane
potential changes that initiate many physiological events
There are ten members of the voltage gated 𝐶𝑎2+
family in mammals
They serve distinct roles in cellular signal transduction
The 𝐶𝑎𝑣1 subfamily initiates contraction, secretion, regulation of gene
expression, integration of synaptic input in neurons, and synaptic transmission
at ribbon synapses in specialized sensory cells
The subfamily 𝐶𝑎𝑣 2 is primarily responsible for initiation of synaptic
transmission at fast synapses
The subfamily 𝐶𝑎𝑣3 is important for repetitive firing of action potential in
rhythmically firing cells such as cardiac myocytes and thalamic neurons
29.
30.
31. Voltage gated CHLORIDE CHANNELS
Unlike 𝐶𝑎2+
, 𝐶𝑙−
does not seem to play a role as intracellular messenger
In mammals, the gene family of chloride channels has nine members that may
function in the plasma membrane or in intracellular compartments
CLC proteins were thought to have probably 10 or 12 transmembrane
domains, 2 nucleotide binding folds(NBFs)
The cellular functions of plasma membrane 𝐶𝑙−
channels may be grouped
Cell volume regulation
Ionic homeostasis
Transepithelial transport
Regulation of electrical excitability
32. Continued..
Ionic homeostasis and cell volume regulation
Cl channels play a crucial role in controlling the ionic composition of cytoplasm
and the volumes of cells
This function is performed in a closed interplay with various ion transporters,
including pumps, co transporters and other ion channels
Crystallographic structural studies of a potassium channel have shown that, when a potential difference is introduced over the membrane, the associated electric field induces a conformational change in the potassium channel. The conformational change distorts the shape of the channel proteins sufficiently such that the cavity, or channel, opens to allow influx or efflux to occur across the membrane. This movement of ions down their concentration gradients subsequently generates an electric current sufficient to depolarize the cell membrane.
Voltage-gated sodium channels and calcium channels are made up of a single polypeptide with four homologous domains. Each domain contains 6 membrane spanning alpha helices. One of these helices, S4, is the voltage sensing helix.[6] The S4 segment contains many positive charges such that a high positive charge outside the cell repels the helix, keeping the channel in its closed state.
In general, the voltage sensing portion of the ion channel is responsible for the detection of changes in transmembrane potential that trigger the opening or closing of the channel. The S1-4 alpha helices are generally thought to serve this role. In potassium and sodium channels, voltage-sensing S4 helices contain positively-charged lysine or arginine residues in repeated motifs.[3] In its resting state, half of each S4 helix is in contact with the cell cytosol. Upon depolarization, the positively-charged residues on the S4 domains move toward the exoplasmic surface of the membrane. It is thought that the first 4 arginines account for the gating current, moving toward the extracellular solvent upon channel activation in response to membrane depolarization. The movement of 10–12 of these protein-bound positive charges triggers a conformational change that opens the channel.[4] The exact mechanism by which this movement occurs is not currently agreed upon, however the canonical, transporter, paddle, and twisted models are examples of current theories.[7]
Movement of the voltage-sensor triggers a conformational change of the gate of the conducting pathway, controlling the flow of ions through the channel.[3]
The main functional part of the voltage-sensitive protein domain of these channels generally contains a region composed of S3b and S4 helices, known as the "paddle" due to its shape, which appears to be a conserved sequence, interchangeable across a wide variety of cells and species. A similar voltage sensor paddle has also been found in a family of voltage sensitive phosphatases in various species.[8] Genetic engineering of the paddle region from a species of volcano-dwelling archaebacteria into rat brain potassium channels results in a fully functional ion channel, as long as the whole intact paddle is replaced.[9] This "modularity" allows use of simple and inexpensive model systems to study the function of this region, its role in disease, and pharmaceutical control of its behavior rather than being limited to poorly characterized, expensive, and/or difficult to study preparations.[10]
Although voltage-gated ion channels are typically activated by membrane depolarization, some channels, such as inward-rectifier potassium ion channels, are activated instead by hyperpolarization.
The gate is thought to be coupled to the voltage sensing regions of the channels and appears to contain a mechanical obstruction to ion flow.[11] While the S6 domain has been agreed upon as the segment acting as this obstruction, its exact mechanism is unknown. Possible explanations include: the S6 segment makes a scissor-like movement allowing ions to flow through,[12] the S6 segment breaks into two segments allowing of passing of ions through the channel,[13] or the S6 channel serving as the gate itself.[14] The mechanism by which the movement of the S4 segment affects that of S6 is still unknown, however it is theorized that there is a S4-S5 linker whose movement allows the opening of S6.[3]
Inactivation of ion channels occurs within milliseconds after opening. Inactivation is thought to be mediated by an intracellular gate that controls the opening of the pore on the inside of the cell.[15] This gate is modeled as a ball tethered to a flexible chain. During inactivation, the chain folds in on itself and the ball blocks the flow of ions through the channel.[16] Fast inactivation is directly linked to the activation caused by intramembrane movements of the S4 segments,[17] though the mechanism linking movement of S4 and the engagement of the inactivation gate is unknown.