1. Intro to Neurobiology 20041 Membrane excitability The action potential

2. Intro to Neurobiology 20042 Outline Passive and active conduction in neurons Action potential phenomenology Participating currents Voltage clamp experiments Voltage dependence: activation and inactivation Qualitative mechanistic description of action potential phenomenology

3. Intro to Neurobiology 20043 Reminder: passive conduction

4. Intro to Neurobiology 20044 Propagation of action potentials Depends on passive membrane properties Conduction velocity increases with λ And decreases with τ

5. Intro to Neurobiology 20045 Improving conduction velocity Increased diameter (squid…) –Problem: limited space Myelin –Increases R m –Decreases C –Allows energetically efficient signaling

6. Intro to Neurobiology 20046 Myelin PNS-Schwann cells –1 per internode CNS- Oligodendrocytes –1 per several axonal processes 10-160 membrane wraps –Cytoplasm is squeezed out

7. Intro to Neurobiology 20047 Saltatory conduction Passive conductance in internodes Active AP regeneration in nodes of Ranvier

8. Intro to Neurobiology 20048 Differential channel constitution

9. Intro to Neurobiology 20049 Demyelination Slowing of conduction Desynchronization of different fibers Conduction block –Complete –At high frequencies

10. Intro to Neurobiology 200410 Conduction velocity Mylinated: –Aα 80-120m/s –Aβ30-80m/s –aδ5-30m/s Unmylinated: –C<2m/s

11. Intro to Neurobiology 200411 Geometrical considerations Theoretically, myelin=0.7 total diameter –Experimentally, 0.6-0.8 Theoretically, internodes should be 100*d –Experimentally they are. Problems may arise at –Sudden expansion of membranes –Branching –Unmyelinated regions Safety factor

12. Intro to Neurobiology 200412 The action potential- phenomenology Rapidly conducting Non-attenuated Fast electrical signal

13. Intro to Neurobiology 200413 Characterized by Voltage overshoot All or none Refractoriness Accommodation phenomena –Accommodation to depolarization –Accommodation to hyperpolarization

14. Intro to Neurobiology 200414 All-or-none Explosive depolarization upon threshold crossing

15. Intro to Neurobiology 200415 Refractoriness Refractory period –Absolute: No amount of current will produce a second action potential –Relative: Second action potential will be achieved with only with larger currents

16. Intro to Neurobiology 200416 Accommodation phenomena Accommodation I –After prolonged depolarization subsequent APs to are Less frequent Smaller Depolarization block –Prolonged hyperpolarization Lowers threshold of action potential Increases its amplitude Anodic break response

17. Intro to Neurobiology 200417 Role of Na + and K +

18. Intro to Neurobiology 200418 Early clues Total conductance is increased during action potential (Cole and Curtis, 1938) Voltage overshoot at the peak of the action potential (Hodgkin and Huxley, 1939) Rapid repolarization of the membrane

19. Intro to Neurobiology 200419 Early findings Action potential amplitude depends on extracellular Na + concentration (Hodgkin and Katz, 1949)

20. Intro to Neurobiology 200420 Participating currents Hodgkin Huxley experiments Captured voltage dependence and kinetics of the participating currents in the squid giant axon

21. Intro to Neurobiology 200421 Recall I ion =g ion (V m -E ion ) g ion =I ion V m -E ion But they are interdependent: g(V m )V m (g) I total =I C +I R

22. Intro to Neurobiology 200422 Voltage clamp setup V m is controlled Vm=Vc After 1 st step

23. Intro to Neurobiology 200423 Voltage clamp experiments I early =I total -I late substitute Na + out with cholineH +

24. Intro to Neurobiology 200424 Or use selective neurotoxins TTX - High affinity voltage dependent Na + channel blocker Saxitoxin -’’- Cocaine – Low affinity voltage dependent Na + channel blocker TEA - Low affinity voltage dependent K + channel blocker

25. Intro to Neurobiology 200425 Na+ and K+ currents Note: direction time course inactivation

26. Intro to Neurobiology 200426 Voltage dependence

27. Intro to Neurobiology 200427 IV curve

28. Intro to Neurobiology 200428 Single channel recordings

29. Intro to Neurobiology 200429 Activation Activation: Increased probablity of channel opening with depolarization Deactivation: decreased probability of channel opening with repolarization

30. Intro to Neurobiology 200430 Peak conductance (V m ) g ion =I ion V m -E ion

31. Intro to Neurobiology 200431 Peak conductance (t)