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Cell and cell signalling



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  • 1. PHysiology of cell and By Tsegay. H. cell signalling By Tsegay. H. 1
  • 2. What is cell? Cells are the smallest structural and functional unit of all living things, Our body is an aggregate of 100 trillions of different cells all working together for the maintenance of the entire organism. A typical cell has two parts: nucleus and cytoplasm. The cytoplasm is separated from the surrounding fluid (ECF) by the plasma membrane. The nucleus is separated from the cytoplasm by a nuclear membrane 2
  • 3. Structural levels of organization of human body Muscle cells Nerve cells Cells: 4 types Epithelial cells Cells in the connective tissues Muscle tissue Tissues 4 types Nerve tissue Epithelial tissue connective tissues Organs: Example: Heart, lungs that are made up of 4 types of tissues Organ system: Example: Respiratory system, CVS Organism: Human organism 3
  • 4.  Cells of different tissues and organs vary in structures and functions; However, there are certain characteristics common to all cells: Growth and development, Irritability, Movement, Reproduction, Excretion 4
  • 5. Parts of the Cell Typical cell has two parts: nucleus and cytoplasm.  The nucleus is separated from the cytoplasm by a nuclear membrane and the cytoplasm is separated from the surrounding fluid (ECF) by the plasma membrane.Cytoplasm The gel-like material within the cell membrane It is a fluid matrix composed of water, salts, organic molecules and many enzymes that catalyze reactions, along with dissolved substances such as proteins and nutrients. 5
  • 6. Functions of cytoplasm Helping to maintain the shape and consistency of the cell Providing suspension to organelles The very specialized structures suspended in the cytoplasm are organelles As site of storage for chemical substances 6
  • 7. 7
  • 8. The nucleus The nucleus is the control center for the cells. It contains the genes, which are hereditary units Chemically each gene consists of highly compressed DNA in the form of chromosomes Genes control cellular activity by determining the type of proteins, enzymes, and other substances that are made by the cell. The nucleus is also the site of RNA synthesis There are three kinds of RNA:  Messenger RNA (mRNA), which carries the instruction from DNA for protein synthesis to the cytoplasm  Ribosomal RNA (rRNA), which moves to the cytoplasm where it becomes the site of protein synthesis  Transfer RNA (tRNA), serves as an amino acid transporter system within the cell for protein synthesis. 8
  • 9.  DNA and RNA are made up of nucleotides  Nucleotides are composed of nitrogen containing bases purine (A, G) and pyrimidin (C, T) as well as deoxyribose sugar conjugated by phosphate.  In RNA, the pyrimidin base T is replaced by U and the 5- carbon sugar is ribose. In addition to the chromatin, the nucleus contains one or two round bodies called nucleoli. It is here that rRNA is synthesized. The nuclear contents are surrounded by a double walled nuclear membrane. The pores present in this membrane allow fluids, electrolytes, RNA, and other materials to move between the nuclear and cytoplasmic comportments. 9
  • 10. Functions of nucleotides2.Building units of nucleic acid (DNA, RNA)3.High energy molecules (ATP, GTP)4.Biosynthetic mediators (UDP-glycogen)5.Regulator of chemical reaction in the cell e.g. cAMP6.Act as coenzyme (NAD, FAD) 10
  • 11. Cellular organelles Are ‘specialized structures suspended in the cytoplasm’ These include the ribosome, endoplasmic reticulum (ER) Golgi apparatus, mitochondria, lysosomes, and the cytoskeletal system (microtabules and microfilaments). Ribosomes Are the sites of protein synthesis in the cell Small particles composed of rRNA and proteins Found in two forms: attached to the wall of ER or as free ribosomes.  Free ribosomes are found in two forms Scattered in the cytoplasm and  Clustered (aggregated) to form functional units called polyribosomes 11
  • 12.  Endoplasmic reticulum (ER)  It is an extensive membranous structure that connects various parts of the inner cell. ER is also connected with the nuclear membrane.  There are two types of ER: rough ER and smooth ER.  The rER is studded with ribosomes. The function of rER is to segregate proteins that are being exported from the cell. o rER =protein synthesis. 12
  • 13. Endoplasmic reticulum (ER) cont……d  The sER is free of ribosome.  Function of sER varies in different cells.  The sarcoplasmic reticulum of skeletal and cardiac muscle cells are forms of sER.  Calcium ions needed for muscle contraction are stored and released from the sarcoplasmic reticulum of muscle cells.  In the liver, the sER is involved in glycogen storage and drug Endoplasmic reticulum (rER and sER) metabolism. o sER can synthesize a group of drug metabolizing enzymes called microsomal system. 13
  • 14.  Golgi Complex= delivery center of the cells The Golgi complex consists of flattened membranous saccules and cisterns that communicate with the ER and acts as a receptacle for hormones and others substances that the ER produces. It then modifies and packages these substances into secretary granules. 14
  • 15.  Mitochondria  The mitochondria are literally the “power plants” of the cell, capable of producing the energy rich compound ATP, which is required for various cellular activities.  The mitochondria require oxygen to produce energy (ATP) from food stuffs. 15
  • 16. Mitochondria 16
  • 17.  Lysosomes  Lysosomes are sac-like compartments that contain a number of powerful digestive enzymes.  They break down harmful cell products and waste materials, cellular debris, and foreign invaders such as bacteria, and then force them out of the cell.  Degrade old dead cells and phagocytosis of microrganisms 17
  • 18.  Cytoskeletal system of the cell  Composed of microfilament and microtubules  Rigid threadlike structures dispersed through out the cytoplasm  Function of cytoskeletal system: • Maintain shape of the cells. • Serve as a transport system for the movement of compounds and organelles within the cell. • Provide for the support and movement of cilia and flagella • Cell to cell contact: to fasten cell membranes together 18
  • 19. The plasma membrane It is a sheet-like structure that surround (enclose) the cell, separating the cellular contents from the ECF. It is entirely composed of proteins and lipids in a ratio of 55:43 respectively, and 3% of carbohydrates. Percent proportion  Proteins: 55 % Phospholipids 25 %  Lipids: 42 % Cholesterol 13 % Neutral fats 4%  Carbohydrate: 3% The level of cholesterol determines rigidity of the membrane 19
  • 20. Function of the plasma membrane Separates cellular contents from the ECF Regulates the passage of substances in and out.  It is semi-permeable allowing some subs to pass through it excluding others. o This creates unequal distribution of ions on both sides of the membrane. It provides receptors for NTs, hormones and drugs. It is a means of cell to cell contact. Plays an important role in the generation and transmission of electrical impulse in nerves muscle. Involved in the regulation of cell growth and proliferation. 20
  • 21. Structure of the cell membrane A plasma membrane is a fluid in its nature, The cell membrane consists of an organized arrangement of proteins, lipids and CHOs1. Lipids: The major lipids are phospholipids such as phosphatidyl choline and phosphatidyl-ethanolamine, and cholesterol. Lipids form the basic structure of the membrane. The lipid molecules are arranged in two parallel raws, forming a lipid bilayer. 21
  • 22. Structure of the cell membrane cont….d The phospholipids component is organized into a double layer with their hydrophobic (tail) directed towards the center of the membrane and polar hydrophilic heads directed out ward facing ECF and ICF. The lipid bilayer portion of the cell membrane is impermeable to water and water soluble substances such as ions, glucose, urea and others. On the other hand, fat soluble substances such as O2, CO2, alcohol and drugs can penetrate this portion of the membrane. 22
  • 23. Structure of the cell membrane cont….d2. Proteins: are two types• Integral or intrinsic proteins:  Interdingitated in the hydrophobic center of the lipid bilayer  Transmembrane proteins are integral proteins that span the entire bilayer.  Transmembrane proteins serve as:  Channels through which ions pass  Carriers which actively transports material. across the bilayer e.g. glucose  Pumps which actively transport ions  Receptors for neurotransmitters and hormones  Integral proteins that are present only on one side of the membrane, serve primarily as enzymes. 23
  • 24. B. Peripheral or extrinsic proteins: Bind to the hydrophilic polar heads of the lipid or on integral proteins. Peripheral proteins that bind to the intracellular surface contribute to the cytoskeleton. Peripheral proteins that bind to the external surface contribute to the glyco-colgx, a cell coat that is composed of glycol-lipids and glycol-proteins to cover the cell membrane 24
  • 25. 3. Carbohydrates Attached invariably on the outside surface of the membrane, binding with protruded integral proteins and lipid, they form glyco-proteins and glyco-lipid (glycocalyx) respectively. They play a role in – Immune reaction (antigenical importance), – Cell to cell attachment and – Act as receptors for NTs, hormones and drugs 25
  • 26. Transport through the cell membrane Substances are transported through the cell membrane by:• Simple diffusion• Osmosis ECF• Facilitated diffusion• Active transport (1O and 2O) and• Vesicular transport ICF mechanisms. 26
  • 27. 1. Simple Diffusion Diffusion is passive movement of substances down their concentration gradient. Factors affecting the net rate of diffusion  Lipid solubility of the substances  Membrane permeability  Concentration difference or Pressure difference  Electrical potential difference of ions Membrane permeability is affected by  Membrane Thickness  Lipid solubility  No of ion channels per unit area  Temperature: T =  thermal motion of molecule permeability  MW 27
  • 28. Simple Diffusion cont….d Rate of diffusion is determined by the following factors summarized in the formula shown below. S. A. T. C Rate of diffusion = D. MWWhere, C = Change of concentration S = Solubility in lipid A = Surface area of the membrane T = Temperature D = Distance or membrane thickness MW = Molecular wt of substances Examples: Substances that are transported by simple diffusion are CO2, O2, alcohol, lipid soluble drugs and ions through specific channels. 28
  • 29. 2. Osmosis It is the power of movement of H2O from an area of higher amount of water to an area of lower amount of water through the semi permeable membrane. The direction of movement of water is governed by the amount of osmoticaly active particles (solutes). The pressure that opposes osmosis of water is called osmotic pressure H2O molecules have very small (0.3 nm) in diameter, so that they can not traverse the lipid bilayer simply. Instead they pass through specific water channels called aquaporins: Five aquapurins (AQ1….AQ5) have been identified in the body. 29
  • 30. 3. Facilitated diffusion Carrier mediated transport Carriers are saturable, do not need energy Glucose Transports substances down their concentration gradient ECF Cell membrane Examples: transport of ICF glucose, proteins. Carrier protein (Macromolecules) 30
  • 31. 4. Active transport Substances are transported against concentration, Common examples electrochemical gradient, up 2. Na+ - K+ ATPase hill direction. 3. H+ - K+ ATPase Used for the transport of Na+, 4. Ca2+ ATPase K+, Ca2+, Fe2+, H+, Cl- Consumes energy in the form of ATPPrimary active transport  Carrier protein are involved  Consumes energy from ATP  Carrier protein is anti- porter 31
  • 32. Secondary active transport Carrier protein are involved Energy is not from ATP, but from other ions Carrier protein is symporterUniport carriers: Carry single substance to one directionAntiport carriers: Carry two substances in opposite directionsSymport carriers: Carry two substances into the same direction 32
  • 33. 5. Visicular transport Vesicles or other bodies in the cytoplasm move macromolecules or large particles across the plasma membrane. Types of vesicular transport include:  Exocytosis: vesicles fuse with the plasma membrane, then releasing their contents to the outside of the cell. 33
  • 34.  Endocytosis: capturing of a substance outside the cell, then the plasma membrane merges to engulf it.  The substance subsequently enters the cytoplasm enclosed in a vesicle. There are two kinds of endocytosis:  Phagocytosis or cellular eating occurs when the dissolved materials enter the cell.  Pinocytosis or cellular drinking occurs when the plasma membrane folds inward to form a channel allowing dissolved substances to enter the cell. 34
  • 35. Intercellular communication The intercellular signaling is subdivided into the following classifications: Neurotransmitters are released by axon terminals of neurons into the synaptic junctions and act locally to control nerve cell functions. Endocrine hormones are released by glands or specialized cells into the circulating blood and influence the function of cells at another location in the body. Neuroendocrine hormones are secreted by neurons into the circulating blood and influence the function of cells at another location in the body. 35
  • 36.  Paracrines are secreted by cells into the ECF and affect neighboring cells of a different type. Autocrines are secreted by cells into the extracellular fluid and affect the function of the same cells that produced them by binding to cell surface receptors. Cytokines are peptides secreted by cells into the extracellular fluid and can function as autocrines, paracrines, or endocrine hormones.  Examples interleukins that are secreted by helper T cells act on other cells of the immune system Cytokine hormones (e.g., leptin) produced by adipocytes are sometimes called adipokines. 36
  • 37. 37
  • 38. Cell junctions The points of contact between two adjacent plasma membranes, cell junctions. There are 3- types of cell junction: Tight junctions Anchoring junctions Communicating junctions 38
  • 39.  Tight junctions Cells are attached tightly with belt like structure so prevent fluid to pass between Are common among epithelial cells of the stomach, intestine, and urinary bladder. They prevent the fluid in a cavity from leaking into the body by passing between cells. 39
  • 40.  Anchoring junctions  Are common in tissues subjected to traction and stretching such as the outer layer of the skin, cardiac muscle, and uterus.  Anchoring junctions include desmosomes, hemidesmosomes and adherence junction.  Adherence junctions connect to microfilaments of the cytoskeleton and link cells to one another or anchor cells to extracellular materials.  Desmosomes form a firm attachment between cells some what like spotwelds. 40
  • 41.  Communicating junctions (Gap junctions)  Are narrow channels that directly connect the cytoplasm of two neighboring cells, consisting of proteins called connexons.  These proteins allow only the passage of ions and small molecules. o Gap junctions allow communication between cells through the exchange of materials or the transmission of electrical impulses. 41
  • 42. Cell junctions 42
  • 43. What tissue mean? Cells of similar function, come together and form higher level of body’s organization, tissue. Cooperative unit of very similar cells that perform a specific function. There are four main types of tissues: o Nervous tissue o Muscle tissue o Connective tissue o Epithelial tissue 43
  • 44. 1.Epithelial Tissue Cells are tightly fitted together in continuous layers, Tight packaging allows tissue to act as a barrier to protect against mechanical injury, infection, and fluid loss, Cover outside of body (skin) and line organs and internal body cavities (mucous membranes of digestive, respiratory, and reproductive systems). 44
  • 45. Epithelial Tissue Covers and Lines the Body and its PartsA. Simple squamous(Lung air sacs) D. Statified squamous (Lining esophagus)B. Simple cuboidal(Kidney tubes)C. Statified columnar(Lining intestine) 45
  • 46. Epithelial tissues, mucous membranes, absorb and secrete chemical solutions. Mucous membranes: – Digestive tract epithelium (mucous membranes) secretes mucus and digestive enzymes. – Respiratory tract epithelium secretes mucous that helps trap dust particles before they reach the lungs. 46
  • 47. 2. Connective Tissue Connective tissues are fibrous tissues Are made up of cells separated by non-living material, which is called extracellular matrix. Functions: As the name implies, connective tissue serves a "connecting" function. It supports and binds other tissues. Gives shape to organs and holds them in place. 47
  • 48. Types of connective tissue A. Loose connective tissue  Most widespread connective tissue  Loose matrix with fibers, packing material  Function: Attaches skin to muscles, binds and holds tissues and organs in place B. Adipose (fat) tissue  Protection  Insulation  Energy storage 48
  • 49. Types of connective tissue cont…..d C. Blood The only fluid connective tissue Composed of plasma having water, plasma proteins, and other substances, and Cellular elements [RBCs, WBCs and platelets] Function: Transporting function Regulatory function [water, temperature, pH…..] Protective function [stoppage of bleeding, engulfing invaders, development of body immunity] 49
  • 50. Types of connective tissue cont…..dD. Fibrous Connective Tissue Matrix of closely packed collagen fibers, Strong and non-elastic, Found in: Tendons: Attach muscles to bones Ligaments: Attach bone to bone 50
  • 51. Types of connective tissue cont…..dE. Cartilage Hard matrix with collagen fibers  Found on end of bones, nose, ears, and between vertebra.F. Bone Supports the body Solid matrix of collagen fibers and calcium, phosphate, and magnesium salts. Bone is harder than cartilage, but not brittle because of collagen. 51
  • 52. Connective Tissue Binds and Provides Support A. Loose Connective Tissue D. Fibrous Connective Tissue B. Adipose Tissue E. Cartilage C. Blood F. Bone 52
  • 53. 3. Muscle TissueMuscle, the most abundant type of tissue, is the fleshy organ of the body that converts potential energy of food into mechanical energy [produce force and movement] to perform different activities.Made up of long cells [sacromers = contractile unit of muscle] that contract when stimulated by nerve impulses.Muscle cells have many microfilaments made up of actin and myosin.Muscle contraction accounts for much of energy consuming work. 53
  • 54.  There are three types of muscle tissue Skeletal (striated) muscle  Located attached to bones by tendons & moves skeleton  They are elongated, cylindrical, multinucleated cells, and striated  Innervated by somatic nerve system  Responsible for voluntary movements. B. Cardiac muscle  Striated, uni or bi nucleated muscles found in walls of the heart forming contractile tissue of heart.  Controlled by autonomic nerve system, drugs and 54
  • 55. C. Smooth muscle Found in walls of visceral organs [digestive tract, bladder, arteries, uterus, and…….] Non-striated and mono-nucleated cells Responsible movement of different activities with in the body. [food, dust particles, child during delivery, urine, sperm, ovum……] Contract more slowly than skeletal muscle, but can remain contracted longer. Controlled by autonomic nerve system, drugs and hormones [are involuntary muscles]. Both cardiac and smooth muscles have authorythamic property, [generate action potential even with out nerve supply] 55
  • 56. Types of Muscle B. Cardiac muscleA. Skeletal muscle C. Smooth muscle 56
  • 57. 4. Nervous Tissue Senses stimuli[receptors], carry sensory information [sensory =afferent pathway] to CNS where it is processed and appropriate information is formulated [association neurons], then transmit the formulated response[motor =efferent pathway] to the glands and muscles[ effector organs] Controls the activity of muscles and glands, and allows the us to respond to its environment. 57
  • 58. Types of nervous tissueNervous tissue made up of two types of cells: Neuron Structural and functional unit of nervous tissue. Consists of: Cell body: Contains cell’s nucleus. Dendrite: Extension that conveys signals towards the cell body. Axon: Extension that transmits signals away from the cell body. Supporting cells(neuroglial cells)  Nourish, protect, and insulate neurons. 58
  • 59. Nervous Tissue Forms a Communication Network
  • 60. Excitable Tissues? The term excitability refers to an ability of a tissues to receive stimuli and respond to that stimuli. Excitable tissues respond to various stimuli by rapidly changing their resting membrane potentials and generating electrochemical impulses (action potential). The stimuli can be electrical, chemical, mechanical or thermal. There are two types of excitable tissues: Nerve Muscle 60
  • 61. 1. Nervous SystemOrganization of the Nervous System 61
  • 62. Nervous System2. Central Nervous System (CNS)  Spinal cord and brain  Function: integrate, process and coordinate sensory input and motor output3. Peripheral Nervous System (PNS)  All neural tissue outside CNS  Function: carry information to and from CNS  Composed of: Cranial nerves (12 pairs) to and from brain Spinal nerves (31 pairs) to and from spinal cord  Nerve = bundle of axons (nerve fibers) with blood vessels and connective tissues. 62
  • 63. Divisions of PNS1. Sensory/Afferent Division  Carry sensory information to CNS  Grouped in to: III.Somatic afferent division  Carry sensory information of voluntary activities like of skin, skeletal muscles, joints IV.Visceral afferent division o Carry sensory information of involuntary activities like glands and smooth muscles of internal organs 63
  • 64. 2. Motor/Efferent Division o Carry information from CNS to effectors o Grouped to:B. Somatic Nervous System  Voluntary nervous system  Carry to skeletal musclesB. Autonomic Nervous System (ANS)  Involuntary nervous system  Carry to smooth & cardiac muscle, glands  Could be:  Sympathetic Division: “fight or flight” Parasympathetic Division: “rest and digest”  They antagonize each other 64
  • 65. Nerve tissue• Two principal cell types that make up the nerve system are neurons and neuroglial cells Neurons are ‘functional units of the nerve system’ o Neurons are specialized for the generation and transmission of nerve impulse. Sensory function Generation of thought Storage of memory Integration of idea Coordination of muscular activities Neuroglial cells: o The neuroglial cells are non excitable cells found in association with neurons. o They provide supporting functions to the neuron. 65
  • 66.  Neuroglial cells outnumber neurons by about 20x  5 types of supporting cells, 4 are found in the CNS: 2. Astrocytes  Star-shaped, abundant, and versatile cells  Guide the migration of developing neurons  Involved in the formation of the blood brain barrier  Function in nutrient transfer  Interconnect blood vessels and nerve fibers. 66
  • 67. Neuroglial cells cont….d2. Microglial cells  Specialized immune cells that act as the macrophages of the CNS3. Ependymal Cells  Line the ventricles of the brain and the central canal of the spinal cord  Some are ciliated which facilitates the movement of cerebrospinal fluid 67
  • 68. 4. Oligo-dendrocytes  Produce the myelin sheath which provides the electrical insulation for neurons in the CNS5. Schwann cells  Form myelin sheaths around the larger nerve fibers in the PNS.  Vital for neuronal regeneration 68
  • 69. Neurons: Functional structures Neurons are functional units of the nervous system. Specialized to conduct information from one part of the body to another A typical neuron has three distinct parts. These are: Dendrites, Cell body & Axon.  Dendrites: Collect information and send it to cell body.  Cell body: Connect dendrites and axon, main bio-synthetic and metabolic center  Axon: Take information away of cell body to another cell 69
  • 70. Neurons: morphological classification Structurally neurons are classified into three classes:• Multipolar neurons(neurons having more than 2 processes) found in the CNS, motor in function• Bipolar neurons (neurons with 2 processes): found in the retina and inner ear• Unipolar neurons (neurons having only one process): sensory in function 70
  • 71. Functional Classification of Neurons Functionally, there are thee classes of neurons: – Sensory(afferent) neurons: conduct impulses from periphery to the central nerve system – Inter-neurons (association or integrative) neuron: o Receive and interpret sensory information o Conduct formulated response to effectors via motor area. – Motor (efferent) neurons: conduct impulses from central nerve system (brain & spinal cord) to the periphery 71
  • 72. Myelin? Is electrically insulating material that forms a layer, the myelin sheath, usually around only the axon of a neuron. Myelin is an outgrowth of glial cell. The production of the myelin sheath is called myelination It is essential for the proper functioning of the nervous system. In humans, the production of myelin begins in the 14th week of fetal development, although little myelin exists in the brain at the time of birth. 72
  • 73. Myelin cont….d• During infancy, myelination occurs quickly and continues through the adolescent stage of life.• Schwann cells supply the myelin for peripheral neurons, whereas oligodendrocytes, myelinate the axons of the central nervous system.Composition of myelin• Myelin may be made by different cell types, varies in chemical composition and configuration, but performs the same insulating function. 73
  • 74. Composition of myelin cont…..d Myelin is about 40 % water;  The remaining dry mass of myelin is about 70 - 85 % lipids and about 15 - 30 % proteins. Some of the proteins that make up myelin are  Myelin basic protein (MBP),  Myelin oligodendrocyte glycoprotein (MOG), and  Proteolipid protein (PLP). The primary lipid of myelin is a glycolipid called galactocerebroside (GalC). The intertwining hydrocarbon chains of sphingomyelin serve to strengthen the myelin sheath. 74
  • 75. Myelination in the CNS Myelination in the PNS 75
  • 76. Myelin cont….dThe wrapping is never completeInterspersed along the axon are gaps wherethere is no myelin – these are nodes of Ranvier.Function of myelin sheath Protects axon Facilitate rate of action potential conduction Saves ATP 76
  • 77. The soma Is where the signals from the dendrites are joined and passed on The soma and the nucleus and organelles do not play an active role in the transmission of the neural signals.  Instead, serve to maintain the cell and keep the neurons functional. The supporting structures of the cell include mitochondria, which provide energy for the cell, and the Golgi apparatus, which packages products created by the cell and secretes them outside the cell wall. 77
  • 78. Soma cont….d Contains nucleus and normal organelles  Biosynthetic center of the neuron Contains a very active and developed rough endoplasmic reticulum which is responsible for the synthesis of NTs.  The neuronal rough ER is referred to as the Nissl body. Contains many bundles of protein filaments (neurofibrils) maintain the shape, structure, and integrity of the cell. 78
  • 79. Soma cont….d Clusters of soma in the CNS are known as nuclei Clusters of soma in the PNS are known as ganglia 79
  • 80. Nerve fiber Is a threadlike extension of a nerve cell A nerve fiber may be myelinated and/or unmyelinated. Found both in the central and peripheral nervous system. Consists of an axon and myelin sheath (if present) in the nervous system. 80
  • 81. Nerve fiber cont…….d In the central nervous system (CNS), myelin is produced by oligodendroglia cells. Schwann cells form myelin sheath in the peripheral nervous system (PNS). Schwann cells can also make a thin covering for an axon which does not consist of myelin (in the PNS)= endoneurium A peripheral nerve fiber consists of an axon, myelin sheath, Schwann cells and its endoneurium. There are no endoneurium and Schwann cells in the central nervous system. 81
  • 82. Classification of nerve fibers1. Central nerve fibers In CNS, nerve fibers differ in terms of size, conduction velocity, and presence or absence of myelin.  For example, the olfactory nerve fibers are short and unmyelinated, but the optic nerve fibers are myelinated A bundle of nerve fibers in CNS constitutes = tract  The pyramidal tract and extra pyramidal tracts have long nerve fibers that descend from the brain to the spinal cord.  These fibers have an important role in motor control, and are known as descending tracts. 82
  • 83.  There are other bundles of nerve fibers in the CNS are called ascending tracts.  These carry sensory information from the periphery to the different areas of the brain.Peripheral nerve fiber types A nerve may be sensory, motor or sensory-motor (mixed). There are three types of nerve fibers in a mixed nerve:  Sensory nerve fibers (afferent fibers)  Motor nerve fibers (efferent fibers) Autonomic nerve fibers Somatic nerve fibers 83
  • 84. Components of peripheral nerve fiber  Each peripheral nerve fiber contains: An axon Axolemma Myelin sheath (if present) Schwanns sheath (neurolemma) Endoneurium, [endoneurial channel, sheath or tube], is a layer of weak connective tissue made up of endoneurial cells that encloses the myelin sheath of peripheral nerve fiber. 84
  • 85. Classification of peripheral nerve fibers There are three types of peripheral nerve fibers based on their diameter and myelination:  A group  B group  C groupA group  Have a large diameter and are myelinated fibers, high conduction velocity, and.  The A group consists of four types of nerve fibers: A alpha fibers (afferent or efferent fibers) A beta fibers (afferent or efferent fibers) A gamma fibers (efferent fibers) A delta fibers (afferent fibers) 85
  • 86. Motor fibers of the A groupA alpha fibers  High conduction velocity.  Alpha motor neurons innervate extrafusal muscle fibersA beta fibers  Beta motor neurons innervate intrafusal muscle fibers of muscle spindles (nuclear bag and nuclear chain fibers), with collaterals to extrafusal muscle fibers.A gamma fibers  Gamma motor neurons innervate intrafusal muscle fibers of muscle spindles (nuclear bag and nuclear chain fibers). 86
  • 87. Sensory fibers of the A groupA alpha fibers (Ia fiber or Ib fibers) Characteristics:  High conduction velocity  Ia fibers are related to muscle spindle primary endings (muscle sense)  Ib fibers are related to golgi tendon organs (muscle sense)A beta fibers (II fibers) II fibers carry sensory information related to muscle spindle secondary endings, touch, and kinesthesia.A delta fibers (III fibers) III fibers carry sensory information related to pain, temperature, crude touch, and pressure. 87
  • 88. B group Are myelinated with a small diameter They are the preganglionic fibers of the autonomic nervous system.  Have low conduction velocity.C group Are unmyelinated and as the B group fibers have a small diameter and low conduction velocity. These fibers include:  Postganglionic fibers in the autonomic nervous system (ANS)  Nerve fibers at the dorsal roots  These fibers carry the following sensory information: pain, temperature, touch, pressure and itch 88
  • 89. Neuronal Processes• Axons: myelinated/unmylinated• Most neurons have a single axon – a long (up to 1m) process designed to convey information away from the cell body.• Originates from a special region of the cell body called the axon hillock.• Transmit APs from the soma toward the end of the axon where they cause NT release.• Often branch sparsely, forming collaterals.• Each collateral may split into telodendria which end in a synaptic knob, which contains synaptic vesicles – membranous bags of 89 NTs.
  • 90. Classification of Ion Channels I. Leak channel II. Gated Channel Na+ channels There are three major types;  Na+ leak channels  Voltage-gated Na+ channels  Ligand (chemical –gated) Na+ channels K+ Channels  There are four major classes: K+- leak channels Voltage-gated K+ channels Ligand- gated K+ channels 90 G-prorein- gated K+ channels
  • 91.  Ca+ Cahnnels  Are the following:  Voltage- gated Ca+ channels with subtypes L-type Ca+- gated channels T- type Ca+- gated channels N-type Ca+- gated channels  Ligand- gated Ca+- gated channels  G- protein-gated Ca+- gated channels 91
  • 92.  The Na+-K+ channel causes large concentration gradients for sodium and potassium across the resting nerve membrane. These gradients are the following:  Na+ outside =142mEq/L, Na+ inside =14mEq.L  K+ outside = 4mEq/L, K+ inside = 140mEq/L  The ratios of these two respective ions from the inside to the outside are Na+ inside/Na+ outside =0.1 K+ inside/K+ outside =35 92
  • 93. • All cells have a voltage difference across their plasma membrane.  This is called membrane potential.• The membrane potential (VM) at rest is called resting membrane potential (RMP)• The RMP of a typical neuron is -90 mv  Meaning, ‘at rest there is more electro-positivity out and electro-negativity inside the cell membrane of the neuron.’ 93
  • 94. Origin of Resting Membrane Potential 1. Leakage of Potassium and Sodium through the Nerve Membrane  The nerve membrane contains channel protein through which potassium and sodium ions can leak, called a potassium-sodium (K+-Na+) "leak" channel. o On average, the channels are far more permeable to potassium than to sodium, normally about 100 times as permeable and hence K+ plays a major role than Na+. 94
  • 95. 2. Contribution of the Potassium Diffusion Potential The diffusion potential level across a membrane that exactly opposes the net diffusion of a particular ion through the membrane is called the Nernst potential for that ion.  The magnitude of Nernst potential is determined by the ratio of the concentration of specific ion on the two sides of the membrane. The greater this ratio, the greater the tendency for the ion to diffuse in one direction, and therefore the greater the Nernst potential required to prevent additional net diffusion. 95
  • 96. • The following equation, called the Nernst equation, can be used to calculate the Nernst potential for ion at normal body temperature of 37°C:• EMF (in mv) is electromotive force EMF=+ 61 log concentration inside concentration out side When using this formula, it is usually assumed that the potential in the extracellular fluid, outside the membrane remains at zero potential, and the Nernst potential is the potential inside the membrane. Thus, when the concentration of positive potassium ions on the inside is 10 times that of the outside, the log of 10 is 1, so that the Nernst potential calculates to be -61 millivolts inside the membrane 96
  • 97.  We make the assumption that the only movement of ions through the membrane is diffusion of potassium ions between inside and outside the membrane. Because of the high ratio of potassium ions inside to outside, 35:1, the Nernst potential = the logarithm of 35 is 1.54, and times -61 millivolts is -94 millivolts. Therefore, if potassium ions were the only factor causing the resting potential, the resting potential inside the fiber would be equal to -94 millivolts. 97
  • 98. 3. Contribution of Sodium Diffusion through the Nerve Membrane. There is slight permeability of the nerve membrane to sodium ions caused by the minute diffusion of sodium ions through the K+-Na+ leak channels. The ratio of sodium ions from inside to outside the membrane is 0.1, and this gives a calculated Nernst potential for the inside of the membrane of +61 millivolts. But the Nernst potential for potassium diffusion is -94 millivolts. How do these interact with each other, and what will be the summated potential? 98
  • 99. Calculation of the Diffusion Potential When the Membrane Is Permeable to Several Different Ions• When a membrane is permeable to several different ions, the diffusion potential that develops depends on three factors: (1) the polarity of the electrical charge of each ion, (2) the permeability of the membrane (P) to each ion, and (3) the concentrations (C) of the respective ions on the inside (i) and outside (o) of the membrane.• Thus, the following formula, called the Goldman equation, or the Goldman-Hodgkin-Katz equation, gives the calculated membrane potential on the inside of the membrane when two univalent positive ions, sodium (Na+) and potassium (K+), and one univalent negative ion, chloride (Cl-), are involved. EMF=-61 log C Na+i P Na+ + C K+i P K+ C Na+o P Na+ + C K+o P K + 99
  • 100. • This can be answered by using the Goldman equation described previously.• Intuitively, one can see that if the membrane is highly permeable to potassium but only slightly permeable to sodium, it is logical that the diffusion of potassium contributes far more to the membrane potential than does the diffusion of sodium.• In the normal nerve fiber, the permeability of the membrane to potassium is about 100 times as great as its permeability to sodium.• Using this value in the Goldman equation gives a potential inside the membrane of -86 millivolts, which is near the potassium potential 100
  • 101. 4. Contribution of the Na+-K+ Pump. The Na+-K+ pump provides an additional contribution to the resting potential. There is continuous pumping of three sodium ions to the outside for each two potassium ions pumped to the inside of the membrane by hydrolyzing one ATP 101
  • 102.  This creates an additional degree of negativity (about -4 millivolts additional) on the inside beyond that which can be accounted for by diffusion alone. There are also negatively charged non-diffusible proteins within the ICF that cannot travel through the membrane.  What this adds up to is the fact that the inside of the cell is negative with respect to the outside.  The interior has less positive charge than the exterior. Therefore, the net membrane potential with all these factors operative at the same time is about -90 millivolts. 102
  • 103. In summary,• The diffusion potentials alone caused by potassium and sodium diffusion would give a membrane potential of about -86 millivolts, almost all of this being determined by potassium diffusion.• Then, an additional -4 millivolts is contributed to the membrane potential by the continuously acting electrogenic Na+-K+ pump, giving a net membrane potential of -90 millivolts.• There are also negatively charged non- diffusible proteins within the ICF that cannot travel through the membrane 103
  • 104. Nerve Action Potential• Nerve action potentials are rapid changes in the resting membrane potential that spread rapidly along the nerve fiber membrane.• Each action potential begins with a sudden change from the normal resting negative membrane potential to a positive potential and then ends with an almost equally rapid change back to the negative potential.• To conduct a nerve signal, the action potential moves along the nerve fiber until it comes to the fibers end. 104
  • 105. The successive stages of the action potential are as follows:• Resting Stage:  This is the resting membrane potential before the action potential begins.  The membrane is said to be "polarized" during this stage because of the -90 mv negative membrane potential that is present.  To explain more fully the factors that cause both depolarization and repolarization, we need to describe the special characteristics of two other types of transport channels through the nerve membrane: the voltage-gated sodium and potassium channels. 105
  • 106. 2. Depolarization Stage: At this time, the membrane suddenly becomes very permeable to sodium ions, allowing tremendous numbers of positively charged sodium ions to diffuse to the interior of the axon. The normal "polarized" state of -90 mv is immediately neutralized by the inflowing positively charged sodium ions, with the potential rising rapidly in the positive direction. This is called depolarization. In large nerve fibers, the great excess of positive sodium ions moving to the inside causes the membrane potential to actually "overshoot" beyond the zero level and to become somewhat positive. In some smaller fibers, as well as in many central nervous system neurons, the potential merely approaches the zero level and does not overshoot to the positive state. 106
  • 107. 3. Repolarization Stage.: Within a few 10,000ths of a second after the membrane becomes highly permeable to sodium ions, the sodium channels begin to close and the potassium channels open more than normal. Then, rapid diffusion of potassium ions to the exterior re- establishes the normal negative resting membrane potential. This is called repolarization of the membrane. K+ channels are slow to open and slow to close. This causes the VM to take a brief dip below resting VM. This dip is the undershoot and is an example of hyperpolarization 107
  • 108. Phases of action potential 108
  • 109. Phases of action potentialB. RMP: causesD. Depolarization: ionic causesF. Repolarisation: ionic causes 109
  • 110. Action potential cont…..d• If membrane potential(VM)reaches threshold, Na+ channels open and Na+ influx =depolarizing the cell and causing the VM to increase.  This is the rising phase of an AP.• Eventually, the Na+ channel will have inactivated and the K+ channels will be open.• Now, K+ effluxes and repolarization occurs.  This is the falling phase. 110
  • 111. Events during an action potential 111
  • 112. Role of action potentials in the transmission of a nerve impulse. A STMULUS causes the Na+ gated channel proteins to open which allows Na+ ions to diffuse down the concentration gradient across the membrane into the cell and so set off an action potential. 112
  • 113. 113
  • 114. 114
  • 115. Voltage-Gated Sodium and Potassium Channels The necessary actor in causing both depolarization and repolarization of the nerve membrane during the action potential is the voltage-gated sodium channel. A voltage-gated potassium channel also plays an important role in increasing the rapidity of repolarization of the membrane.Voltage-Gate The voltage-gated sodium channel has two gates-one near the outside of the channel called the activation gate, and another near the inside called the inactivation gate. 115
  • 116. They have 2 gates  At rest, one is closed (the activation gate) and the other is opened (the inactivation gate).  Suprathreshold depolarization affects both of them. 1 2 116
  • 117. 3 4 5 117
  • 118. Activation of the Sodium Channel When the membrane potential becomes less negative than during the resting state, rising from -90 millivolts toward zero, it finally reaches a voltage-usually somewhere between -70 and -50 millivolts-that causes a sudden conformational change in the activation gate, flipping it all the way to the open position. This is called the activated state; during this state, sodium ions can pour inward through the channel, increasing the sodium permeability of the membrane as much as 500- to 5000-fold. 118
  • 119. Initiation of the Action PotentialA Positive-Feedback Cycle Opens the Sodium Channels. First, as long as the membrane of the nerve fiber remains undisturbed, no action potential occurs in the normal nerve. However, if any event causes enough initial rise in the membrane potential from -90 mv toward the zero level, the rising voltage itself causes many voltage-gated sodium channels to begin opening. 119
  • 120. Initiation of the Action Potential cont……d This allows rapid inflow of sodium ions, which causes a further rise in the membrane potential, thus opening still more sodium channels and allowing more streaming of sodium ions to the interior of the fiber. This process is a positive-feedback cycle ,  Continues until all the voltage-gated sodium channels have become opened. Then, within another fraction of a millisecond, the rising membrane potential causes closure of the sodium channels as well as opening of potassium channels, and the action potential soon terminates.  120
  • 121. Threshold for Initiation of the Action Potential:• An action potential will not occur until the initial rise in membrane potential is great enough to create the vicious cycle described in the preceding paragraph.• This occurs when the number of Na+ ions entering the fiber becomes greater than the number of K+ ions leaving the fiber.• A sudden rise in membrane potential of 15 to 30 millivolts usually is required.• Therefore, a sudden increase in the membrane potential in a large nerve fiber from -90 millivolts up to about -65 millivolts usually causes the explosive development of an action potential.• This level of -65 millivolts is said to be the threshold for stimulation. 121
  • 122. Propagation of the Action Potential• An action potential elicited at any one point on an excitable membrane usually excites adjacent portions of the membrane, resulting in propagation of the action potential along the membrane.• When a nerve fiber is excited in its mid-portion-that is, the mid-portion suddenly develops increased permeability to sodium, and there will be current flow from the depolarized areas of the membrane to the adjacent resting membrane areas.• That is, positive electrical charges are carried by the inward- diffusing sodium ions through the depolarized membrane and then for several millimeters in both directions along the core of the axon.• This transmission of the depolarization process along a nerve or muscle fiber is called a nerve or muscle impulse. 122
  • 123. Propagation of Action Potential• Continuous (sweeping) conduction (occurs in unmyelinated axons)  In this situation, the wave of de- and repolarization simply travels from one patch of membrane to the next adjacent patch.  APs moved in this fashion along the sarcolemma of a muscle fiber as well. 123
  • 124. 2. Saltatory (jumping) conduction (occurs in myelinated axons)• Recall that the myelin sheath is not completed.  There exist myelin free regions along the axon, the nodes of Ranvier.• The wave of depolarization and repolarization jump from nodes of Ranvier to nodes of RanvierAdvantages Increase speed of transmission by 100 folds. Conserve energy as sodium-potassium pump only has to operate at the nodes and fewer ions have to be transported 124
  • 125. Rates of AP Conduction Depends Upon• Level of myelination  Faster in mylinated than in unmyelinated2. Size of nerve fiber  Faster in large sized than in smaller ones3. Age slower in babies and in elderly  Maximum b/n the age 5-15 years4. Temperature  which affects the rate of diffusion and the rate of energy release by respiration for active transport (since it is controlled by enzymes)  the consequence is that nerve impulse transmission is faster in endothermic animals which maintain a high body temperature. 125
  • 126. Properties of the action potential Action potentials have a threshold:  This is the minimum level of stimulus necessary to cause depolarisation (i.e. open the ion channels) Action potentials have all -or -nothing principle:  Once an action potential has been produced at any point on the membrane of a normal fiber, the depolarization process travels over the entire membrane if conditions are right, or it does not travel at all if conditions are not right. This is called the all-or-none principle, and it applies to all normal excitable tissues. 126
  • 127. Properties of the action potential cont....d Has refractory Periods During the time interval between the opening of the Na+ channel activation gate and the opening of the inactivation gate, a Na+ channel cannot be stimulated. This is called refractory period. There are two types of refractory period:5. Absolute refractory period (ARP)6. Relative refractory period (RRP)Absolute refractory period (ARP):  Interval b/n the opening of the Na+ channel activation gate and the opening of the inactivation gate.  2nd action potential can not be generated regardless of the strength of stimulus. 127
  • 128. • ARP begins at the start of up stroke (the activated Na+ channels start as fast as possible) and extends into the downward stroke (Na+ channels are inactivated) .• A Na+ channel cannot be involved in another AP until the inactivation gate has been reset.Relative Refractory Period(RRP) New action potential can occur in an excitable fiber if the stimulus is supra threshold The stimulus should be greater than normal b/c there are still inactivated sodium channels and more K+ channels than normal are still open. The RRP begins when the ARP ends.  Reason: Number of inactivated Na+ channels and Activated K+ channels during RRP. 128
  • 129. Graded Potentials also called receptor potentials Local changes in membrane potential Upon being stimulated, the dendrites of a neuron produce a graded potential. Stimulation can occur in many ways, including chemical stimulation (neurotransmitters, etc.), mechanical stimulation (certain pain receptors, hair receptor, etc.), light stimulation (photoreceptors) and a few other methods. Magnitude of change is related to magnitude of triggering event 129
  • 130. Triggering event Triggering event causes a flow of ions across the membrane Leads to localized change in membrane potential Without constant triggering event, graded potentials will die out Current is local – does not spread very far; and is small, <10mV change Depending on the strength of the stimulus, can be changed to AP usually on summation. 130
  • 131. Comparison between Graded potential and action potentialsGraded potential Action potential Graded responses-Amplitude varies  All or none response; once a with condition of the initiating membrane is depolarized to events threshold, amplitude is independent of the initiating event.Graded responses can be summated Action potential can not be summatedHas no refractory period Has refractory periodIs conducted decrementally; amplitude Not affected by distancedecreases with distanceDuration varies Duration is constant with a specific cell under constant conditionCan be depolarization or repolariztion Is depolarization with an overshootInitiated by environmental stimulus Initiated by membrane depolarization.(receptor) ,by NTs, or spontaneously 131
  • 132. Synaptic Transmission Synapse is the junction b/n two cells in which one must be a neuron. It is the site of transmission from one neuron to the next. Is site where neuron communicates with another cell: (neuron or effectors) There 3 types of synapses 1. Neuroneuronal junction (presynaptic and postsynaptic neurons) 2. Neuromuscular junction 3. Neuroglandualr junction  There 3 types of neuroneuronal junctions i.e. o Axo-dendritic, o Axosomatic and o Axo-axonic junctions 132
  • 133.  In autonomic NS, they are called ganglia (ganglion singular)  Pre- synaptic structure is always a nerve  Post- synaptic structure can be: • A nerve • Muscle • Gland • Skin The post- synaptic structures are collectively called effector organs or simply effectors. 133
  • 134. 134
  • 135. Synaptic Transmission Begins with the stimulation of a neuron.  One neuron may be stimulated by another, by a receptor cell, or even by some physical event such as pressure. Once stimulated, a neuron will communicate information about the causative event.  Such neurons are sensory neurons and they provide info about both the internal and external environments.  Sensory neurons (afferent neurons) will send info to neurons in the brain and spinal cord.  There, association neurons (interneurons) will integrate the information and then perhaps send commands to motor neurons (efferent neurons) which synapse with muscles or glands. 135
  • 136.  Thus, neurons need to be able to conduct information in 2 ways:  From one end of a neuron to the other end (pre and post synaptic neurons). Accomplished electrically via APs  Across the minute space separating one neuron from another (synapse) Accomplished chemically via neurotransmitters. One neuron will transmit information to another neuron or to a muscle or gland cell by releasing chemicals called neurotransmitters. 136
  • 137.  The site of this chemical interplay is known as the synapse.  An axon terminal (synaptic knob) will adjoin another cell, a neuron, muscle fiber, skin, or gland cell.  This is the site of transduction – the conversion of an electrical signal into a chemical signal.Mechanism of transmission An AP reaches the axon terminal →open VG-Ca2+ channels →Ca2+ rushes in and binds to regulatory proteins → initiation of NT exocytosis. NTs diffuse across the synaptic cleft bind to receptors on the postsynaptic membrane → initiation of some sort of response on the postsynaptic cell. 137
  • 138. Mechanism of transmission 138
  • 139. Mechanism of Synaptic Transmission• An AP reaches the presynaptic axon terminal of the presynaptic cell and causes V-gated Ca2+ channels to open.• Ca2+ rushes in, binds to regulatory proteins & initiates NT release by exocytosis.• NTs diffuse across the synaptic cleft and then bind to specific receptors on the postsynaptic membrane and initiate postsynaptic potentials.• NT-receptor interaction results in either EPSP or IPSP  Different neurons can contain different NTs.  Different postsynaptic cells may contain different receptors.  Thus, the effects of NT can vary. 139
  • 140. Mechanism of Synaptic Transmission When the NT-R combination triggers the opening of ligand-gated Na-channels, this leads to membrane depolarization, EPSP. E.g. Ach on Nicotinic receptor When the NT-R combination triggers the opening of ligand gated K+ or Cl- channels, this leads to membrane hyperpolarization, IPSP e.g. GABA on GABAb receptor 140
  • 141. EPSPs & IPSPs Graded hyperpolarization Graded depolarizationBring the neuronal VM closer to Bring the neuronal VM fartherthreshold. away fromThus, it’s often referred to as anexcitatory postsynaptic potential or threshold andEPSP. thus are referred to as inhibitory postsynaptic potentials or IPSPs. 141
  • 142. Summation• One EPSP is usually not strong enough to cause an AP• However, EPSPs may be summedA. Temporal summation  The same pre-synaptic neuron stimulates the postsynaptic neuron multiple times in a brief period.  The depolarization resulting from the combination of all the EPSPs may be able to cause an AP.B. Spatial summation  Multiple neurons all stimulate a postsynaptic neuron resulting in a combination of EPSPs which may yield an AP 142
  • 143. 143
  • 144. 144
  • 145. Neurotransmitter Removal NTs are removed from the synaptic cleft via:  Enzymatic degradation  Diffusion  Reuptake 145
  • 146. Properties of synaptic transmission4. Unidirectional conduction5. Synaptic delay (0.5 -1.0m/s)6. Fatigue -↓in response of postsynaptic neurons after repetitive stimulation by the presynaptic neurons7. Synaptic potentiation (facilitation):– persistence of out put signals after the stoppage of in put signal 146
  • 147. Factors Affecting Synaptic transmission pH  Alkalosois ↑ Synaptic transmission  Acidosis ↓ Synaptic transmission Hypoxia ↓ Synaptic transmission Drugs  Caffeine, theophylline, theobromine ↑ Synaptic transmission  Strychinine ↑ Synaptic transmission  Hypnotics, anesthtics, tranquilizers ↓ Synaptic transmission 147