1. Introduction to Neurochemistry I Presentation by Josh Morrison for Biochemistry II February 21, 2005

2. The Membrane Potential Vm is the symbol for Membrane Potential Vm is the electrical charge of a cell Present in all cells

3. Importance of Vm Source of potential energy for transporting ions and molecules across cell membrane i.e. Na/glucose cotransporter Determines if ion will be actively or passively transported across membrane Thus, to some extent, determines how cell will spend energy

4. Origin of Vm Vm is complex interaction between ion concentrations and the channels and pumps through which ions enter and exit cell To help understand the factors involved, let us look at a simple cell with only one positive and one negative ion

5. Simple Cell Recall physics. For electricity to exist, there must be a complete pathway for electron flow. Ion=charged particle (like electron). Thus, flow of ions equals electric flow.

6. Simple cell con’t Let’s say that the positive ion flows through channel from high concentration to low concentration (selective permeability) However, flow of charged particle causes electrical charge of cell to shift (from neutral to positive) Shift in electrical properties of cell disfavors flow of positive charge out of cell

7. Flow of ions in simple cell Lecture #2 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec /lectures.asp

8. Nernst Equation E ion =(RT)/(zF) log [ion] o / [ion] i Or E ion =58/charge log [ion] o / [ion] i

9. Nernst Equation Predicts Vm value for cell whose membrane is permeable to one ion Example calculation for K+ E K = 58/+1 log [5mM] / [125mM] = -81 mV Limits of Nernst

10. Wrap Up of Vm Real cells are permeable to many different ions Membrane’s permeability to ions major factor in determining what Vm (illustrated by Goldman-Hodgkin-Katz Eq.) Thus, the most conductant ion will have the greatest effect on Vm

11. Resting Potential Lecture #2 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

12. Spike Initiation Zone

13. Myelin is actually Schwann cell wrapped around axon multiple times

14. The Action Potential

15. Action Potentials Mode of Communication in Neurons Intensity (frequency) determines magnitude of response Initiation-Propagation-Termination

16. Initiation Occurs only in SIZ Initially, only leak channels open (K+) Slight depolarization to threshold opens Voltage-gated Na channels (VG Na C) Na flows with electrochemical gradient, causing further depolarization All-or-none response

17. Action potential initiation S.I.Z. Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

18. Propagation Local Circuit Currents—Na diffuses down axon and depolarizes other places in axon AP Initiate in these nearby areas Saltatory conduction of AP due to myelin

19. Propagation Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

20. Voltage Gated K channels also in area around node Potassium leak channels present throughout neuron VG Na C found only on the nodes

21. Termination VGNaC inactivate—cause repolarization At the same time, the depolarization has cause VGKC to open—speed repol Flow of K out of cell causes hyperpolarization Refractory Period—prevents “backwards” movement of AP

22. Action potential termination Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp

23. Ig loop (H-gate)

24. http://wilkes-fs1.wilkes.edu/~terzaghi/BIO-226/lectures/13.html Role of S4 helix in gating

25. Activation of sodium channel through S4 movement (M-gate) Outside Cytosol Ready state: No Na entry (Vm=-70 mV) Active State: Na enters (Vm=threshold) depol time

26. H-gate inactivates sodium channel once Vm cytosol becomes positive Ready Inactive Active H-gate M-gate Lecture #5 From Dr. James A. Murray’s Website http://faculty.uca.edu/%7Ejmurray/BIOL4425/lec/lectures.asp Na+