1. Announcements Midterm –Saturday, October 23, 4:30pm Office Hours cancelled today

2. Today Action Potentials continued –Aside about voltage-gated ion channels Action Potential Conduction

3. K+ Na+ Voltage-gated channels K+ leak channel Na+ K+ Section of Squid Axon Membrane Potential time

4. Stimulus & Threshold The stimulus depolarizes the membrane –Experimentally applied current –Synaptic potential –Receptor potential

5. Threshold The membrane potential at which Na flowing into the cell exactly equals the K flowing out of the cell A fraction more stimulus depolarization is required to ‘fire’ an action potential

6. Threshold Potential 0 mV -80 mV Small stimulus Vm below threshold Larger stimulus Vm above threshold

7. Membrane depolarization Increased Na permeability Na+ entry Positive Feedback  AP is regenerative  displays all-or-none behaviour Stimulus

8. Why does the AP stop rising? 1.As Vm  E Na, Na+ inflow stops 2.Na+ channels inactivate 3.K+ channels open, K+ outflow starts E Na

9. Refractory Period 1.A second stimulus very soon after the first will not fire an AP (Absolute) 2.With a delay, a second stronger stimulus will cause a small AP (Relative) 3.With longer delay a second AP can be fired

10. Absolute refractory period Relative refractory period A B C

11. Why is there Refractory Period? The Na channel stays inactivated for a short period of time after it closes Inactivated Open Closed Active Closed Active

12. Summary & Key Concepts 1.The AP is controlled by rapid changes in ionic permeability 2.Permeability is a function of voltage- gated ion channels 3.Threshold potential 4.Positive feedback 5.Refractory period has two phases

13. Voltage-gated ion channels –Transmembrane protein that forms a pore that ions can pass through –Usually very specific for an ion –Opening is controlled by Vm Depolarization causes channel to open –Closing is a property of the channel Some close quickly Some stay open

14. + + + + + + + + + + + + + + + + _ _ _ _ + + + + K+K+

15. Action Potential Conduction Axon hillock Region of neuron where AP usually starts

16. Action Potential Conduction Why are Action Potentials needed? 1.First look at current flow without APs. 2.Second look at current with APs

17. Announcements Tutorial tonight 5pm ARC

18. Passive Current Flow Record voltage Inject +’ve current axon

19. voltage distance 0.63V 0 0 Length constant

20. Passive Current 1.Current decays very rapidly along the length of an axon 2.The length constant is the distance over which the potential drops to 63% of the highest value 3.Typical length constants range only from 1-5 mm

21. Length Constant Depends on: 1.Resistance across the membrane (‘leakiness’) 2.Longitudinal resistance to current flow (varies with axon diameter)

22. Passive Current Flow Inject current axon Membrane Resistance Longitudinal Resistance

23. Action Potential Conduction Record voltage Stimulate Action Potential axon

24. Action Potential Conduction 1.APs constant amplitude at all points along the axon

25. Na+ Inject current

26. Na+ Inject current

27. Sequence of Events leading to AP propagation 1.Stimulus opens Na+ channels & cause AP 2.Depolarizing current flows down the axon 3.Local depolarization opens Na+ channels downstream & initiate a new AP 4.Na+ channels close (inactivate) & K+ channels open 5.Local depolarization opens Na+ channels downstream and initiate a new AP

28. Na+ Inject current

29. Conduction Velocity Record voltage Inject current axon Measure distance between recording sites Measure time between APs

30. 1.Axon diameter 2.Myelination Small unmyelinated  0.5 m/s Large myelinated  120 m/s

31. Myelinated nerve Myelin Formed by: Schwann cells (periphery) Oligodendrocytes (central) Node of Ranvier

32. Myelin

33. Na+ Saltatory conduction

34. Myelin Myelin increases speed of conduction by: 1.Increasing membrane resistance Reduces ‘leakiness’   length constant 2.Voltage-gated channels only at Node of Ranvier APs generated only at the Node

35. Mulitple Sclerosis Demyelination of axons –Impaired AP conduction –Symptom depends on nerves affected Optic nerve  blindness Motor nerves  weakness or paralysis

36. Summary & Key Concepts 1.Currents flow passively down axon decay described by length constant 2.Action potentials propagation due to sequential opening of Na+ channels in response to local depolarization 3.Conduction velocity determined by axon diameter and myelination - length constant 4.Myelin  trans-membrane resistance and places Na+ channels only at Nodes Saltatory conduction