Caltech Bi 211 Fall 1999

Revised 9/29/99
Course announcement
Tentative Schedule
Requirements

Session 3
Tuesday
10/12
7:00 PM
234 Kerckhoff

Nicotinic
Acetylcholine Receptor
Superfamily

1.Sarah Farivar

Readings in Hille

Chapter 6
Chapter 9, pp 236-250
Chapter 16, pp 423-434.

Additional Required Readings

Miyazawa, A., Y. Fujiyoshi, M. Stowell and N. Unwin 1999. Nicotinic acetylcholine receptor at 4.6 A resolution: transverse tunnels in the channel wall. J Mol Biol. 288:765-86.
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The state of the art on 3-dimensional structure of channels; and a mechanism for opening

Pascual, J. M. and A. Karlin 1998. State-dependent accessibility and electrostatic potential in the channel of the acetylcholine receptor. Inferences from rates of reaction of thiosulfonates with substituted cysteines in the M2 segment of the a subunit. J Gen Physiol. 111:717-39.
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Pascual, J. M. and A. Karlin 1998. Delimiting the binding site for quaternary ammonium lidocaine derivatives in the acetylcholine receptor channel. J Gen Physiol. 112:611-21.
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These two papers illustrate classic tactics: mapping a channel with cysteine reagents and with open-channel blockers

Zhou, M., A. G. Engel and A. Auerbach 1999. Serum choline activates mutant acetylcholine receptors that cause slow channel congenital myasthenic syndromes. Proc Natl Acad Sci U S A. 96:10466-10471.
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A disease of nicotinic receptors, analzysed at the single-channel level

Figl, A., N. Viseshakul, N. Shafaee, J. Forsayeth and B. N. Cohen 1998. Two mutations linked to nocturnal frontal lobe epilepsy cause use-dependent potentiation of the nicotinic ACh response. J Physiol (Lond). 513:655-70.
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A CNS disease of nicotinic receptors, analyzed at the single-channel level