1 V m = the Value of the Na Battery Plus the I Na is Isolated By - PDF document

Voltage-Gated Ion Channels and the Voltage-Gated Ion Channels and the Action Potential Action Potential • The Action Potential jdk3 – Generation – Conduction Principles of Neural Science, chaps 8&9 • Voltage-Gated Ion Channels – Diversity – Evolutionary Relationships Equivalent Circuit of the Membrane Electronically Generated Current Counterbalances the Na + Membrane Current Connected to the Voltage Clamp I m Command VC I mon g = I/V PNS, Fig 9-2 For Large Depolarizations, I K is Isolated By Blocking I Na Both I Na and I K Are Activated PNS, Fig 9-3 PNS, Fig 9-3 1

V m = the Value of the Na Battery Plus the I Na is Isolated By Blocking I K Voltage Drop Across g Na I m VC PNS, Fig 9-3 g Na and g K Have Two Similarities and Two Differences Calculation of g Na V m = E Na + I Na /g Na I Na = g Na (V m - E Na ) g Na = I Na /(V m - E Na ) PNS, Fig 9-3 PNS, Fig 9-6 Voltage-Gated Na + Channels Have Three States Total I Na is a Population Phenomenon PNS, Fig 9-3 PNS, Fig 9-9 2

The Action Potential is Generated by Na + Channels Open in an All-or-None Fashion Sequential Activation of g Na and g K PNS, Fig 9-10 PNS, Fig 9-12 Local Circuit Flow of Current Contributes to Negative Feedback Cycle Underlies Action Potential Propagation Falling Phase of the Action Potential Increased gK + Na + Inactivation Slow Open Na + Channels Fast Depolarization Inward I Na PNS, Fig 8-6 Conduction Velocity Can be Increased by Myelin Speeds Up Increased Axon Diameter and by Myelination Action Potential Conduction Increased Axon r a dV/dt I Diameter Myelination C m dV/dt + + + + + + + + ∆ V = ∆ Q/C - - - - - - - - PNS, Fig 8-8 3

Opening of Na + and K + Channels is Sufficient to Voltage-Gated Ion Channels and the Generate the Action Potential Action Potential Rising Phase Falling Phase Na + Channels Close; • The Action Potential Na + Channels Open K + Channels Open – Generation – Conduction Na + + - - - - • Voltage-Gated Ion Channels + - - + - - - - - - + + + + + – Diversity + + - - + K + + – Evolutionary Relationships - - - + - + + - - + + + + - + + - - - - - - - + + - - - - + + Na + However, a Typical Neuron Has Several Functional Properties of Voltage-Gated Types of Ion Channels Vary Widely Voltage-Gated Ion Channels • Selective permeability + - - • Kinetics of activation + + - - - - • Voltage range of activation - - - - + + - - - - • Physiological modulators + + - - + Functional properties of Voltage-Gated Voltage-Gated Ion Channels Differ in their Ion Channels Vary Widely Selective Permeability Properties • Selective permeability Cation Permeable Anion Permeable • Kinetics of activation Na + Cl - K + • Voltage range of activation Ca ++ • Physiological modulators Na + , Ca ++ , K + 4

Voltage-Gated K + Channels Differ Widely in Their Functional properties of Voltage-Gated Ion Channels Vary Widely Kinetics of Activation and Inactivation • Selective permeability V • Kinetics of activation • Voltage range of activation I • Physiological modulators Time The Inward Rectifier K + Channels and HCN Voltage-Gated Ca ++ Channels Differ in Channels Are Activated by Hyperpolarization Their Voltage Ranges of Activation Probability of Channel Opening Probability of Channel Opening Physiological Modulation Functional properties of Voltage-Gated Ion Channels Vary Widely • Selective permeability • Kinetics of activation • Voltage range of activation • Physiological modulators: e.g., phosphorylation, binding of intracellular Ca ++ or cyclic nucleotides, etc. 5

HCN Channels That Are Opened by Voltage-Gated Ion Channels Belong to Hyperpolarization Are Also Modulated by cAMP Two Major Gene Superfamilies +cAMP I. Cation Permeant Probability of Channel Opening II. Anion Permeant -120 -90 -60 Voltage-Gated Ion Channel Gene Superfamilies Voltage-Gated Ion Channel Gene Superfamily I) Channels With Quatrameric Structure Related to I) Channels With Quatrameric Structure Related to Voltage-Gated, Cation-Permeant Channels: Voltage-Gated, Cation-Permeant Channels: A) Voltage-gated: A) Voltage-gated: •K + permeant •K + permeant •Na + permeant •Na + permeant •Ca ++ permeant •Ca ++ permeant •Cation non-specific permeant •Cation non-specific permeant (HCN) Structurally related to- B) Cyclic Nucleotide-Gated (Cation non-specific permeant) C) K + -permeant leakage channels D) TRP Family (cation non-specific) ; Gated by various stimuli, such as osmolarity, pH, mechanical force, ligand binding and temperature The α -Subunits of Voltage-Gated Channels Have Been Cloned Voltage-Gated Cation-Permeant Channels Have a Basic Common Structural Motif That is Repeated Four- fold PNS, Fig 6-9 PNS, Fig 9-14 6

Inward Rectifier K + Channels Have Only Four-Fold Symmetry of Voltage-Gated Channels Two of the Six Alpha-Helices per Subunit Arises in Two Ways K + Channels, HCN Channels Na + or Ca ++ Channels I IV II III x4 I IV III II PNS, Fig 6-12 Leakage K + Channels Are Dimers of P-Loops Form the Selectivity Filter of Voltage-Gated Cation-Permeant Channels Subunits With Two P-Loops Each PNS, Fig 6-12 PNS, Fig 9-15 Voltage-Gated Cl - Channels Differ in Voltage-Gated Ion Channel Sequence and Structure from Cation- Gene Superfamilies Permeant Channels II) “CLC” Family of Cl - -Permeant Channels (dimeric structure): Gated by: •Voltage - particularly important in skeletal muscle •Cell Swelling •pH 7

Voltage-Gated Cl - Channels are Dimers x2 8