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Rates and equilibria at the acetylcholine receptor of electrophorus electroplaques. A study of neurally evoked postsynaptic currents and of voltage-jump relaxations

Sheridan, Robert E. and Lester, Henry A. (1977) Rates and equilibria at the acetylcholine receptor of electrophorus electroplaques. A study of neurally evoked postsynaptic currents and of voltage-jump relaxations. Journal of General Physiology, 70 (2). pp. 187-219. ISSN 0022-1295. PMCID PMC2228462. doi:10.1085/jgp.70.2.187.

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Kinetic measurements are employed to reconstruct the steady-state activation of acetylcholine [Ach] receptor channels in electrophorus electroplaques. Neurally evoked postsynaptic currents (PSCs) decay exponentially; at 15°C the rate constant, α, equals 1.2 ms^(-1) at 0 mV and decreases e-fold for every 86 mV as the membrane voltage is made more negative. Voltage-jump relaxations have been measured with bath-applied ACh, decamethonium, carbachol, or suberylcholine. We interpret the reciprocal relaxation time 1/τ as the sum of the rate constant α for channel closing and a first-order rate constant for channel opening. Where measureable, the opening rate increases linearly with [agonist] and does not vary with voltage. The voltage sensitivity of small steady-state conductances (e- fold for 86 mV) equals that of the closing rate α, confirming that the opening rate has little or no additional voltage sensitivity. Exposure to α-bungarotoxin irreversibly decreases the agonist-induced conductance but does not affect the relaxation kinetics. Tubocurarine reversibly reduces both the conductance and the opening rate. In the simultaneous presence of two agonist species, voltage-jump relaxations have at least two exponential components. The data are fit by a model in which (a) the channel opens as the receptor binds the second in a sequence of two agonist molecules, with a forward rate constant to 10^(7) to 2x10^(8) M^(-1)s^(-1); and (b) the channel then closes as either agonist molecule dissociates, with a voltage-dependent rate constant of 10^(2) to 3x10^(3)s^(-1).

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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1977 Rockefeller University Press. Received for publication 12 July 1976. We thank D. Williams for assistance with the animals and dissections, W. L. Crowder and P. Goodeve for help with the computer, F. Sigworth for building the voltage clamp, J. Heesemann for a gift of suberyldicholine, E. Neher for a discussion of edge effects, and D. D. Koblin for participating in some of the experiments. This work was supported by National Institutes of Health grant NS-11756; by a grant-in-aid from the Muscular Dystrophy Association, Inc.; by an Alfred P. Sloan fellowship to H. A. Lester; and by a National Science Foundation predoctoral fellowship to R. E. Sheridan.
Funding AgencyGrant Number
Muscular Dystrophy AssociationUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
Issue or Number:2
PubMed Central ID:PMC2228462
Record Number:CaltechAUTHORS:20120119-120416762
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ID Code:28863
Deposited On:19 Jan 2012 21:37
Last Modified:09 Nov 2021 17:01

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