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Voltage-Gated Ion Channels and the Action Potential

Voltage-Gated Ion Channels and the Action Potential. jdk3. Principles of Neural Science, chaps 8&9. Voltage-Gated Ion Channels and the Action Potential. The Action Potential Generation Conduction Voltage-Gated Ion Channels Diversity Evolutionary Relationships.

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Voltage-Gated Ion Channels and the Action Potential

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  1. Voltage-Gated Ion Channels and theAction Potential jdk3 Principles of Neural Science, chaps 8&9

  2. Voltage-Gated Ion Channels and theAction Potential • The Action Potential • Generation • Conduction • Voltage-Gated Ion Channels • Diversity • Evolutionary Relationships

  3. Electronically Generated Current Counterbalances the Na+ Membrane Current Command g = I/V PNS, Fig 9-2

  4. Equivalent Circuit of the MembraneConnected to the Voltage Clamp Im VC Imon

  5. For Large Depolarizations, Both INa and IK Are Activated PNS, Fig 9-3

  6. IK is Isolated By Blocking INa PNS, Fig 9-3

  7. INa is Isolated By Blocking IK PNS, Fig 9-3

  8. Vm = the Value of the Na Battery Plus theVoltage Drop Across gNa Im VC

  9. Calculation of gNa Vm = ENa + INa/gNa INa = gNa (Vm - ENa) gNa = INa/(Vm - ENa) PNS, Fig 9-3

  10. gNa and gK HaveTwo Similarities and Two Differences PNS, Fig 9-6

  11. Voltage-Gated Na+ Channels Have Three States PNS, Fig 9-9

  12. Total INa is a Population Phenomenon PNS, Fig 9-3

  13. Na+ Channels Open in an All-or-None Fashion PNS, Fig 9-12

  14. The Action Potential is Generated bySequential Activation of gNa and gK PNS, Fig 9-10

  15. Negative Feedback Cycle Underlies Falling Phase of the Action Potential Increased gK+ Na+ Inactivation Slow Open Na+ Channels Fast Inward INa Depolarization

  16. Local Circuit Flow of Current Contributes toAction Potential Propagation PNS, Fig 8-6

  17. Conduction Velocity Can be Increased by Increased Axon Diameter and by Myelination Increased Axon Diameter ra dV/dt I Myelination Cm dV/dt + + + + + + + + ∆V = ∆Q/C - - - - - - - -

  18. Myelin Speeds UpAction Potential Conduction PNS, Fig 8-8

  19. Voltage-Gated Ion Channels and theAction Potential • The Action Potential • Generation • Conduction • Voltage-Gated Ion Channels • Diversity • Evolutionary Relationships

  20. + + + + + + + + + Opening of Na+ and K + Channels is Sufficient to Generate the Action Potential Rising Phase Falling Phase Na + Channels Close; K+ Channels Open Na + Channels Open Na + - - - + + - - - + + + + - K+ + + - - + + - + + - + + - - - + + - - Na +

  21. However, a Typical Neuron Has Several Types ofVoltage-Gated Ion Channels + - + + - - - - + + - - + + - +

  22. Functional Properties of Voltage-GatedIon Channels Vary Widely • Selective permeability • Kinetics of activation • Voltage range of activation • Physiological modulators

  23. Voltage-Gated Ion Channels Differ in theirSelective Permeability Properties Cation Permeable Na+ K+ Ca++ Na+, Ca++, K+ Anion Permeable Cl -

  24. Functional properties of Voltage-GatedIon Channels Vary Widely • Selective permeability • Kinetics of activation • Voltage range of activation • Physiological modulators

  25. Voltage-Gated K+ Channels Differ Widely in Their Kinetics of Activation and Inactivation V I Time

  26. Functional properties of Voltage-GatedIon Channels Vary Widely • Selective permeability • Kinetics of activation • Voltage range of activation • Physiological modulators

  27. Voltage-Gated Ca++ Channels Differ in Their Voltage Ranges of Activation Probability of Channel Opening

  28. The Inward Rectifier K+ Channels and HCN Channels Are Activated by Hyperpolarization Probability of Channel Opening

  29. Functional properties of Voltage-GatedIon 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.

  30. Physiological Modulation

  31. HCN Channels That Are Opened by Hyperpolarization Are Also Modulated by cAMP +cAMP Probability of Channel Opening -120 -90 -60

  32. Voltage-Gated Ion Channels Belong toTwo Major Gene Superfamilies I. Cation Permeant II. Anion Permeant

  33. Voltage-Gated Ion Channel Gene Superfamilies I) Channels With Quatrameric Structure Related to Voltage-Gated, Cation-Permeant Channels: A) Voltage-gated: •K+ permeant •Na+ permeant •Ca++ permeant •Cation non-specific permeant

  34. Voltage-Gated Ion Channel Gene Superfamily I) Channels With Quatrameric Structure Related to Voltage-Gated, Cation-Permeant Channels: A) Voltage-gated: •K+ permeant •Na+ permeant •Ca++ 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

  35. The a-Subunits of Voltage-Gated ChannelsHave Been Cloned PNS, Fig 6-9

  36. Voltage-Gated Cation-Permeant Channels Have a Basic Common Structural Motif That is Repeated Four-fold PNS, Fig 9-14

  37. Four-Fold Symmetry of Voltage-Gated Channels Arises in Two Ways K+ Channels, HCN Channels Na+ or Ca++ Channels I IV II III x4 I IV III II

  38. Inward Rectifier K+ Channels Have Only Two of the Six Alpha-Helices per Subunit PNS, Fig 6-12

  39. Leakage K+ Channels Are Dimers of Subunits With Two P-Loops Each PNS, Fig 6-12

  40. P-Loops Form the Selectivity Filter of Voltage-Gated Cation-Permeant Channels PNS, Fig 9-15

  41. Voltage-Gated Ion ChannelGene Superfamilies II) “CLC” Family of Cl--Permeant Channels (dimeric structure): Gated by: •Voltage - particularly important in skeletal muscle •Cell Swelling •pH

  42. Voltage-Gated Cl- Channels Differ in Sequence and Structure from Cation-Permeant Channels

  43. Voltage-Gated Cl- Channels are Dimers x2

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