Ion Channels are responsible for the membrane potential.

1. Ion Channels are responsible for the membrane potential. When the ion channel is closed, there is no potential difference across the cell membrane

2. Ion Channels are responsible for the membrane potential. When the cation-selective ion channel opens, cations will diffuse through, whereas anions will not

3. Ion Channels are responsible for the membrane potential. The crossing-over of cations will create a potential difference (voltage) across the cell membrane.

4. Simulation of membrane:

5. The Nernst Potential. These qualitative demonstrations can be put in more quantitative terms using the Nernst Equation, which relates the voltage V across the membrane which is in equilibrium with the concentration gradient established by the concentrations Co, outside, and Ci, inside.

6. Utility of learning about Nernst potentials: Characterization of mechanisms of disease. In This case: - Learning more about a new ion channel that causes neurons to die during anoxia.

8. Utility of learning about reversal potentials

9. Characterization of a cation current in anoxic neurons

10. Back to the Axon & How it works • Ion Channels • Concepts of Diffusion • Basic Concepts of Electricity • How to Put 1-3 Together

11. Equivalent circuit of the membrane Cm = membrane capacitance (in pF) Rm = membrane resistance Em = Vm = Trans-membrane potential difference Rm = 1/Gm Gm = membrane conductance

12. Generation of the AP The action potential is produced through the sequential activation and inactivation of sodium and potassium channels in the axon. As the membrane depolarizes, Na channels open, allowing an inward Na current to occur. Then, K Channels open, to repolarize the cell while Na Channels inactivate.

13. Generation of the AP

14. Generation of the AP

15. Generation of the AP

16. Generation of the AP

17. Generation of the AP

18. Generation of the AP

19. Propagation of the AP Must now take into account the 3D geometry of the Axon.

20. Propagation of the AP Simplified into an equivalent circuit that can be mathe-matically analyzed

21. Simulation: AP Propagation

22. We have covered: • Ion Channels • Concepts of Diffusion • Basic Concepts of Electricity • How to Put 1-3 Together to get propagation of nerve imulses Now: Back to our patient…..

23. The Arterial Line is in …

24. Now we have to put the patient to sleep: General Anesthesia

25. Now we have to put the patient to sleep: General Anesthesia

26. Now we have to put the patient to sleep: General Anesthesia

27. Now we have to put the patient to sleep: General Anesthesia

28. How General Anesthesia is done: • Give patient something to make them sleep (Anesthetic) • Give patient something to relax (muscle relaxant) • Intubate / Ventilate • Monitor them throughout the surgery

29. General Anesthetics: Are compounds that depress excitatory brain activity, accentuate inhibitory brain activity, or both. • Can be administered as: • Inhalational compounds (Halothane, Isoflurane, Enflurane) • IV compounds (Barbiturates, Propofol, Ketamine, Opiates).

30. Mechanisms of action: Inhalational Anesthetics Textbook Explanation: “The exact mechanism by which inhalational anesthetics function is not known. There appears to be a correlation between anesthetic potency and lipid solubility (Meyer-Overton theory), suggesting that these anesthetics likely affect the lipid matrix of nerve cell membranes in the brain. Furthermore, NMR and electron spin resonance studies indicate that anesthetics cause a local disordering of the lipid membrane matrix, possibly decreasing the number of molecules that alternate simultaneously between the gel and crystalline states, and thereby altering membrane function”. Halothane

31. Mechanisms of action: Intravenous Anesthetics Diverse mechanisms of action, depending on the drug (Benzodiazepines, Opiates, Propofol, etc…) Diazepam Fentanyl Ketamine Propofol

32. However, they all affect Synaptic Activity.