V m = the Value of the Na Battery Plus the Voltage Drop Across g Na. I Na is Isolated By Blocking I K. and g K

Transcription

1 VoltageGated Ion Channels and the Action Potential VoltageGated Ion Channels and the Action Potential jdk3 Principles of Neural Science, chaps 8&9 The Action Potential Generation Conduction VoltageGated Ion Channels Diversity Evolutionary Relationships Electronically Generated Current Counterbalances the Na Membrane Current Equivalent Circuit of the Membrane Connected to the Voltage Clamp I m Command VC g = I/V I mon PNS, Fig 92 For Large Depolarizations, Both I Na and I K Are Activated I K is Isolated By Blocking I Na PNS, Fig 93 PNS, Fig 93 1

2 I Na is Isolated By Blocking I K V m = the Value of the Na Battery Plus the Voltage Drop Across g Na I m VC PNS, Fig 93 Calculation of g Na g Na and g K Have Two Similarities and Two Differences 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 93 PNS, Fig 96 VoltageGated Na Channels Have Three States Total I Na is a Population Phenomenon PNS, Fig 99 PNS, Fig 93 2

3 Na Channels Open in an AllorNone Fashion The Action Potential is Generated by Sequential Activation of g Na and g K PNS, Fig 912 PNS, Fig 910 Negative Feedback Cycle Underlies Falling Phase of the Action Potential Local Circuit Flow of Current Contributes to Action Potential Propagation Increased gk Na Inactivation Slow Open Na Channels Depolarization Fast Inward I Na PNS, Fig 86 Conduction Velocity Can be Increased by Increased Axon Diameter and by Myelination Increased Axon Diameter r a I dv/dt Myelin Speeds Up Action Potential Conduction Myelination C m dv/dt V = Q/C PNS, Fig 88 3

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

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

6 HCN Channels That Are Opened by Hyperpolarization Are Also Modulated by camp VoltageGated Ion Channels Belong to Two Major Gene Superfamilies Probability of Channel Opening camp I. Cation Permeant II. Anion Permeant VoltageGated Ion Channel Gene Superfamilies I) Channels With Quatrameric Structure Related to VoltageGated, CationPermeant Channels: A) Voltagegated: K permeant Na permeant Ca permeant Cation nonspecific permeant VoltageGated Ion Channel Gene Superfamily I) Channels With Quatrameric Structure Related to VoltageGated, CationPermeant Channels: A) Voltagegated: K permeant Na permeant Ca permeant Cation nonspecific permeant (HCN) Structurally related to B) Cyclic NucleotideGated (Cation nonspecific permeant) C) K permeant leakage channels D) TRP Family (cation nonspecific); Gated by various stimuli, such as osmolarity, ph, mechanical force, ligand binding and temperature The αsubunits of VoltageGated Channels Have Been Cloned VoltageGated CationPermeant Channels Have a Basic Common Structural Motif That is Repeated Fourfold PNS, Fig 69 PNS, Fig 914 6

7 FourFold Symmetry of VoltageGated Channels Arises in Two Ways Inward Rectifier K Channels Have Only Two of the Six AlphaHelices per Subunit K Channels, HCN Channels Na or Ca Channels I II III IV x4 I II IV III PNS, Fig 612 Leakage K Channels Are Dimers of Subunits With Two PLoops Each PLoops Form the Selectivity Filter of VoltageGated CationPermeant Channels PNS, Fig 612 PNS, Fig 915 VoltageGated Ion Channel Gene Superfamilies VoltageGated Cl Channels Differ in Sequence and Structure from Cation Permeant Channels II) CLC Family of Cl Permeant Channels (dimeric structure): Gated by: Voltage particularly important in skeletal muscle Cell Swelling ph 7

8 VoltageGated Cl Channels are Dimers x2 8