Voltage gated sodium ion channels are transmembrane proteins that open in response to changes in the electric field across the cell membrane. They are responsible for initiating action potentials in neurons and other excitable cells. The channel is composed of alpha and beta subunits. The alpha subunit forms the core of the channel and has four homologous domains, each with six transmembrane alpha helices. The beta subunits modulate the kinetics of activation. The selectivity filter of the channel is highly selective for sodium ions over other ions. The channel undergoes conformational changes between resting, activated, and inactivated states to regulate the flow of sodium ions.
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.
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.
cellular level understanding of potassium channels, molecular levels, K+ channels, drugs on potassium channels, transmission of potassium across membrane, cell transport system, types of potassium channels, voltage gated, ligand gated, tandem pore
Ion channels have many features of typical membrane proteins. They are synthesized and inserted into the membrane of the endoplasmic reticulum, glycosylated in the Golgi, and transported and inserted into target membranes by membrane fusion. They are regulated by trafficking, phosphorylation, ubiquitination, reversible interactions with other signaling proteins and second messengers, proteolytic cleavage, and other modifications. Like other signaling proteins, ion channels are flexible molecules that undergo conformational changes between open (active) and closed (inactive) states. They evolve and increase in number through phylogeny and can be placed in gene families and super families according to their sequence similarities.
DRUGS AFFECTING THE SODIUM CHANNEL BOTH BLOCKER AND OPENERS, STRUCTURE OF SODIUM CHANNEL AND ITS LOCATION. SODIUM CHANNEL GATTING MECHANISM BY WITCH THEY ACTING. TYPES OF SODIUM CHANNEL AND ITS FUCTIONS. THEIR THERAPEUTIC APPLICATION WITH EXAMPLES OF DRUGS.
1. ION CHANNELS
2. ION CHANNEL RECEPTORS- PRINCIPLES
3. STRUCTURE OF ION CHANNEL RECEPTORS
4. VOLTAGE GATED ION CHANNELS
5. LIGAND GATED ION CHANNELS
6. THANKS
cellular level understanding of potassium channels, molecular levels, K+ channels, drugs on potassium channels, transmission of potassium across membrane, cell transport system, types of potassium channels, voltage gated, ligand gated, tandem pore
Ion channels have many features of typical membrane proteins. They are synthesized and inserted into the membrane of the endoplasmic reticulum, glycosylated in the Golgi, and transported and inserted into target membranes by membrane fusion. They are regulated by trafficking, phosphorylation, ubiquitination, reversible interactions with other signaling proteins and second messengers, proteolytic cleavage, and other modifications. Like other signaling proteins, ion channels are flexible molecules that undergo conformational changes between open (active) and closed (inactive) states. They evolve and increase in number through phylogeny and can be placed in gene families and super families according to their sequence similarities.
DRUGS AFFECTING THE SODIUM CHANNEL BOTH BLOCKER AND OPENERS, STRUCTURE OF SODIUM CHANNEL AND ITS LOCATION. SODIUM CHANNEL GATTING MECHANISM BY WITCH THEY ACTING. TYPES OF SODIUM CHANNEL AND ITS FUCTIONS. THEIR THERAPEUTIC APPLICATION WITH EXAMPLES OF DRUGS.
1. ION CHANNELS
2. ION CHANNEL RECEPTORS- PRINCIPLES
3. STRUCTURE OF ION CHANNEL RECEPTORS
4. VOLTAGE GATED ION CHANNELS
5. LIGAND GATED ION CHANNELS
6. THANKS
Why do ion channels not function like open poresWhat is membrane .pdfjaronkyleigh59760
Why do ion channels not function like open pores?
What is membrane potential?
How do K+ leak channels work? Why is the membrane potential of a resting cell negative?
What is patch clamp recording? What is one of the major insights gained from patch clamp
reporting experiments?
Compare and contrast the three types of gated ion channels.
Be familiar with the different parts of a neuron.
During an action potential, what happens to the membrane potential, voltage-gated Na+
channels, Na+ ions, voltage gated K+ channels, K+ ions, and Na+-K+ ion pumps?
When an action potential reaches a synapse, what happens to the Ca2+ channels, Ca2+ ions,
neurotransmitters, transmitter-gated ion channels, and the post synaptic neuron?
What effect do excitatory or inhibitory neurotransmitters have on postsynaptic cells?
What is an example of a mechanically gated ion channel?
Solution
1.Excitable cells, such as fast-acting neurons and muscle cells, have specialized channels that
open in response to a signal and permit rapid ion movement across the cell membrane. The
opening of just a single ion channel alters the electrical charge on both sides of the membrane.
The resulting charge differential then causes adjacent voltage-sensitive channels to open in
chain-reaction fashion, creating a self-propagating electrical signal that travels down the entire
length of the cell. Sometimes, this sequence of events is triggered when a chemical signal —
such as a neurotransmitter — binds to an ion channel receptor on cell\'s surface. Other times, a
cell\'s ion channels open in response to mechanical (rather than chemical) stimuli.
2.In cells of all types, there is an electrical potential difference between the inside of the cell and
the surrounding extracellular fluid. This is termed the membrane potential of the cell. When a
nerve or muscle cell is at \"rest\", its membrane potential is called the resting membrane
potential. In a typical neuron, this is about –70 millivolts (mV). The minus sign indicates that the
inside of the cell is negative with respect to the surrounding extracellular fluid.
3.The leak channels allow K+ to move across the cell membrane down their gradients (from a
high concentration toward a lower concentration).
With the combined ion pumping and leakage of ions, the cell can maintain a stable resting
membrane potential and create membrane potential of a resting cell negative.
4.Patch clamp recording is an extremely useful technique for investigating the biophysical
properties of the ion channels that control neuronal activation.
The procedure involves pressing a glass micropipette against a cell in order to isolate a small
“patch” of membrane that contains one or more ion channels.
The experimental setup further allows scientists to “clamp” the electrical environment of the
patched area by precisely controlling the voltage across the cell membrane, which, depending on
the ion channels present, impacts the flow of ions through the membrane and allow for int.
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This presentation was uploaded with the author’s consent.
2. Types of channel
Ligand gated ion channel : These channels open when two or more molecules like
neurotransmitter, secreted from nerve terminal bind to the channel
Voltage gated ion channel : Open in response to step changes in the electric field
Mechanically gated ion channel : Open in response to pressure from outside on the membrane
or some kind of deformations
3. Sodium Channels are
Trans membrane proteins responsible for the voltage-dependent increase in sodium
permeability
Responsible for initiations of actions potentials in neurons and other excitable cells
Target for drugs used in the treatment of epilepsy, cardiac arrhythmias
4. Structure
Composed of α, β subunits
Α subunit consist four homologous domain, each with 6 α helical trans membrane subunits
An α subunit form core of the channel and function on its own
Β subunit displays altered voltage dependence and cellular localizations
Highly conserved S4 subunit act as a voltage sensors domain
Consist inactivation gate
Selectivity filter
5. Structure of α subunit
Mainly consist 6 subunits in each homologous domain
Ion conductions is carried out mainly through pore which is selective in nature
Pore domain is divided into two portions i.e. external part and inner pore
External portions is formed by P-loops that connect S5-S6 subunits
Inner pore is formed by the combined S5-S6 subunits from each domain
All subunits are linked to each other
6.
7. Structure of β subunit
Subunit β1 is non-covalently bounded, has four cysteine in its extracellular domain that
contribute Ig like fold
Subunit β1 abundantly present in muscles, heart, and brain
Subunit β2 is covalently bounded, has five extracellular cysteine and form a disulphide bond to
the α subunit
Subunit β2 forms a single intracellular carboxyl terminal domain and a large glycosylated
extracellular domain
Functioning of β subunits is to modulate the kinetics of activations
8. Selective for sodium ion
Selective filter is made up of negatively charged amino acid residue, which attract only positively
charged sodium ion instead of negative ions like chloride
Pore size is about 0.5 nm, which is enough for passage of a single sodium ion with water
molecule
9. States of sodium ion channel
Resting stage : At this stage, activations gate is closed and inactivation gate is open
Activated stage : Passage of sodium ion takes place in this stage, gate is open in activation stage.
Inactivated stage : Channel remains closed in this stage, no passage of ion
10. Function
Mediate fast depolarization
Conduct electrical impulses throughout nerves, muscles and heart
Target for various type of drug and neurotoxin
Responsible for hormonal secretions
14. Key features of sodium ion channel
Voltage dependent activations
Rapid inactivation
Selective ion conductance
15. Sodium channel activations
Change in transmembrane potentials results in conformations change in sodium channel
Change in conformations of S4 helices leading to the opening of channel
Rearrangement of S5 and S6 helices
Result in ion conduction
16. References
Hille B: Ion Channels of Excitable Membranes. third ed. Sunderland, MA: Sinauer Associates;
2001.
Catterall WA: From ionic currents to molecular mechanisms: the structure and function of
voltage-gated sodium channels. Neuron 2000, 26:13-25.
Stock L, Delemotte L, Carnevale V, Treptow W, Klein ML: Conduction in a biological sodium
selective channel. J Phys Chem B 2013, 117:3782-3789.
Michael L.klein.;Treptow.W.;Carnevale.V.;Conductions in a biological sodium
channel.J.phys.chem.B 2013,117,3782-3789.
Barber.F.;Raju.S.G.;Carnevale.;Klein.L.;Hinge-bending motions in the pore domain of a bacterial
voltage-gated sodium channel.J.bbamem.2012.
Klein.l.Michael.;Treptow.;Computer Simulations of Voltage-Gated Cation Channel.J.phys.chem
Lett.2013;3;1017-1023.
17. References
Kuyucak;Mahdavi.S.;Mechanism of Ion Permations in Mammalian Voltage-Gated Sodium
Channel.journal.pone.2015.
Delemotte.L.;Tarek.;Omega Currents in Voltage-Gatrd Ion Channel.vol.46.2013,2755-2762.
Gong.Haipeng.;Li.Yang.;Theoretical and simulations studies on Voltage-Gated sodium
Channel.2015.
Klein.L.;Carnevale.;Small molecule modulations of voltage gated sodium channel.2017, 43,156-
162.
Gong.Haipeng.;Li.Yang.;Liu.Huihui.;The mechanism of Sodium-Potassium selectivity in
mammalian Voltage-Gated Sodium Channel Based on Molecular Dynamics
Simulations.2013.;Biophysical.jouranal.104,2401-2409.
Duclohier.Herve.;Structure-Function studies on the voltage-gated sodium
channel.2009.;Biochimica et Biophysica Acta.2374-2379.