1. 1 Bi/CNS 150 Lecture 4 Wednesday, October 7, 2013 Action potentials Henry Lester

2. Electricity is a Language of the Brain. Intracellular recording with sharp glass electrodes. 1. A current applied by the experimenter increases firing rates V, I https://medicine.yale.edu/lab/mccormick/movies/ Prof. David McCormick’s data

3. Chemistry is also a language of the brain. 2. Artificially applied acetylcholine acts on muscarinic receptors to change the membrane potential, increasing action potential frequency. (The spikes in these examples are about 100 mV in amplitude) https://medicine.yale.edu/lab/mccormick/movies/ V Prof. David McCormick’s data

4. 4 Today’s lecture employs electrical circuits See also Appendix A in Kandel Review your material from Phys 1b, practical

5. 5 Atomic-scale structure of (bacterial) Na + channels (2011, 2012) Views from the extracellular solution electrically, open channel= conductor Views from the membrane plane

6. 6 The miniature single-channel conductors add in parallel E Na (+60 mV) G Na =  Na = G Na  Na outside cytosol = inside mostly K + mostly Na + G K =  K E K (- 60 mV) GKGK KK KK

7. 7 C E G Na +  V EGEGEG GGG KKNa Cl KNaCl    K+K+ At DC, I C = CdV/dt = 0, so Cl - peak of action potential: Na + channels open too resting potential: K + channels open outside cytosol = inside The membrane potential at steady state (not at equilibrium) “after-hyperpolarization”: more K + channels open

8. 8 http://nerve.bsd.uchicago.edu/ Simulation of the nerve impulse (“unclamped”) Francisco Bezanilla's simulation program at the Univ of Chicago:

9. 9 Spatially homogeneous membrane (“membrane AP”). Either spherical, or patch, or wire in axon. First, show passive properties of membrane Turn off conductances. Ampl ± 2, delay 10, duration 15, total time 40 Now back to default (“reset parameters”) Note threshold. Vary pulse amplitude (2 to 20  A). Note constant amplitude Note hyperpolarization. Plot G(K), G(Na) and note that hyperpolarization is caused by G(K). “Refractory” period 30 ms total time, vary pulse 2 duration, pulse 3 = 30  A. Plot G(K) simultaneously. Simulation of the nerve impulse (“unclamped”)

10. 10 Repetitive firing: the frequency code total time to 40 ms; lengthen pulse 1 to 30 ms, Vary pulse amp from 2, 5, 10. Note the smaller AP’s—the squid axon is not specialized for repetitive firing. (For robust frequency encoding, we require at least one additional type of K + channel.) Simulation of the nerve impulse (“unclamped”)

11. 11 http://nerve.bsd.uchicago.edu/nerve1.html Click on Voltage Plot, V vs T. Start Parameter edits are not useful. Cable properties of the Axon Francisco Bezanilla's simulation program at the Univ of Chicago:

12. 12 http://nerve.bsd.uchicago.edu/nerve1.html Propagation(V vs. t) Measure propagation velocity: set blue electrode at 2 cm 6.18 ms – 3.88 ms = 2.3 ms 30 mm/2.3 ms = 11 mm/ms = 13 m/s. Pretty fast! At 30 o C, 2.89 ms - 1.47 ms = 1.42 ms 30 mm / 1.42 ms = 21.1 m/s. Faster Simulation of the nerve impulse (“unclamped”)

13. 13 There are dozens of V-gated channels, Causing the variety of action potential waveforms

14. 14 An approximate explanation for the electrocardiogram, slide 1 The left ventricle pumps against the greatest resistance therefore it has thickest walls; therefore its currents are the largest; therefore it contributes most of the ECG.

15. 15 An approximate explanation for the electrocardiogram, slide 2 C E G Na + K+K+ Cl - extracellular cytosol C E G Na + K+K+ Cl - The capacitive currents are largest An extracellular electrode pair records IR drops proportional to the (absolute value) of the 1st derivative of membrane potential.

16. 16 chest leg Only a small fraction of the current flows across the resistance between chest and a limb. This produces a  V ~ 10 3 times smaller than the transmembrane potential. The ECG records this signal An approximate explanation for the electrocardiogram, slide 3 C E G Na + K+K+ Cl-Cl- extracellular intracellular C E G Na + K+K+ Cl-Cl-

17. 17 Action potentials and the electrocardiogram Electrocardiogram measured on the skin Action Potential measured with intracellular electrode P S R T Q K + channels conductNa + channels conduct ~ 100  V ~ 100 mV ~ 1 sec ST depression is a common anomaly, implying that additional current flows between sections of the heart during the “plateau”

18. 18 -from sense organs to the brain -within the brain -from the brain to muscles -even in a muscle or in the heart -even in the pancreas The frequency of impulses represents signaling among cells in the nervous system.

19. 19 End of Lecture 4

20. 20 Intracellular recording with sharp glass electrodes A cell is receiving stimuli from other cells, not from the experimenter (The spikes in these examples are about 100 mV in amplitude) Same data; choice of formats. Media player required http://info.med.yale.edu/ne urobio/mccormick/movies/rl y_exp.mpg http://info.med.yale.edu/neu robio/mccormick/movies/rly _exp.avi V