Monday April 9, 2014. N ervous system and biological electricity II 1. P re -lecture quiz

1. Monday April 9, 2014. Nervous system and biological electricity II 1. Pre-lecture quiz 2. A review of resting potential and Nernst equation 3. Goldman equation 4. Action potential

2. Information flow through neurons Nucleus Dendrites Collect electrical signals Cell body Integrates incoming signals and generates outgoing signal to axon Axon Passes electrical signals to dendrites of another cell or to an effector cell

3. Neurons form networks for information flow

5. Animation of resting potential • https://www.youtube.com/watch?v=YP_P6bYvEjE

6. Outside of cell Increasing [K+] outside the neuron Microelectrode 0 mV Equilibrium! K channel Increasingly negative charge inside the neuron –65 mV Inside of cell

8. The Nernst equation can be used to calculate the equilibrium potential of a given ion at 20° C

9. Squidhave axons about 1,000 X wider than humans. This allowed them to do the early experiments that provided critical insights into how neurons work. Alan Hodgkin Andrew Huxley

10. Squid Neuron - Continued Important Point #1: They measured actual membrane potential (E-membrane) for the squid axon. voltage meter SW Emembrane-measured = -65 mV axon 0.1mm diameter nerve 1mm diameter

11. Squid Neuron - Continued Important Point #2: They measured the concentrations of Na+, K+, and Cl- inside the squid neuron and outside of it. Emembrane-measured = -65 mV voltage meter SW axon 0.1mm diamter nerve 1mm diameter

12. Squid Neuron - Continued Important Point #2: They measured the concentrations of Na+, K+, and Cl- inside the squid neuron and outside of it. What is the predicted membrane potential based on each of these ions? To answer . . . we simplify the Nernst equation to the following for Na+ and K+. For Cl-, we alter the ratio due to the negative charge (valence). The formula is the following . . . Remember: -log (x) = log (1/x)

13. What's the e-membrane potential based on K+? A. -75mV B. +75 mV C. -173mV D. -1.3 mV E. +173mV

14. Squid Neuron - Continued Important Point #2: They measured the concentrations of Na+, K+, and Cl- inside the squid neuron and outside of it. Predicted E-membrane from Nernst Emembrane -K+= -75 mV E membrane-Na+= 55 mV Emembrane- Cl-= -60 mV Measured E-membrane Emembrane-measured = -65 mV

15. Squid Neuron - Solution Solution: We need a way to consider the effects of all 3 ions on the membrane potential. Will the sum of these predicted values equal the measured membrane potential? Predicted E-membrane from Nernst Emembrane -K+= -75 E membrane-Na+ = 55 Emembrane- Cl- = -60 Emembrane-sum= -80 Measured E-membrane Emembrane-measured = -65 mV

16. Calculating the total resting potential – the Goldman Equation The Goldman Equation extends the Nernst Equation to consider the relative permeabilities of the ions (P): Ions with higher P have a larger effect on Emembrane at 20° C Permeabilitieschange during an action potential and how this allows neurons to “fire”.

17. More key points on equilibrium & membrane potential • The equilibrium potential for an ion is the voltage at which the concentration and electrical gradients acting on that ion balance out. • The Nernst equation is a formula that converts energy stored in a concentration gradient to the energy stored as an electrical potential. This is calculated independently for each ion. • The Goldman equationcalculates a membrane potential by combining the effects of key individual ions.

18. The Action Potential Is a Rapid Change in Membrane Potential 1.Depolarization phase 2.Repolarization phase Threshold potential Resting potential 3.Hyperpolarization phase

19. Outside of cell Increasing [K+] outside the neuron Microelectrode 0 mV Equilibrium! K channel Increasingly negative charge inside the neuron –65 mV Inside of cell

20. Voltage-gated sodium channels allow the action potential to occur • https://www.youtube.com/watch?v=ifD1YG07fB8

21. Voltage-gated channels Two important types: 1.) Na+ voltage gated channels 2.) K+ voltage gated channels How voltage-gated channels work Conformational changes open voltage-gated channels when the membrane is depolarized. At the resting potential, voltage- gated Na+ channels are closed.

22. Patch Clamping Allows Researchers to Record from Individual Channels Currents through isolated channels can be measured during an action potential. Na+ inflow K+ outflow Inward current from Na+ channels Outward current from K+ channels

23. Resting Potential - Both voltage gated Na+ and K+ channels are closed.

24. Initial Depolarization - Some Na+ channels open. If enough Na+ channels open, then the threshold is surpassed and an action potential is initiated.

25. Na+ channels open quickly. K+ channels are still closed. PNa+ > PK+

26. Na+ channels self-inactivate, K+ channels are open. PK+ >> PNa+

27. Emembrane≈ E K+ PK+ > PK+ at resting state

28. Resting Potential - Both Na+ and K+ channels are closed.

30. Action Potentials Propagate because Charge Spreads down the Membrane PROPAGATION OF ACTION POTENTIAL Axon Neuron 1. Na+ enters axon. 2. Charge spreads; membrane “downstream” depolarizes. Depolarization at next ion channel 3. Voltage-gated channel opens in response to depolarization.

34. Action Potentials Propagate Quickly in Myelinated Axons Action potentials jump down axon. Action potential jumps from node to node Axon Nodes of Ranvier Schwann cells (glia) wrap around axon, forming myelin sheath Schwann cell membrane wrapped around axon

35. Wider axons have higher conduction velocities. Myelinated axons have higher conduction velocities.