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Response of acetylcholine receptors to photoisomerizations of bound agonist molecules

Nass, Menasche M. and Lester, Henry A. and Krouse, Mauri E. (1978) Response of acetylcholine receptors to photoisomerizations of bound agonist molecules. Biophysical Journal, 24 (1). pp. 135-160. ISSN 0006-3495. PMCID PMC1473870. doi:10.1016/s0006-3495(78)85352-1.

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In these experiments, agonist-induced conductance is measured while a sudden perturbation is produced at the agonist-receptor binding site. A voltage-clamped Electrophorus electroplaque is exposed to trans-Bis-Q, a potent agonist. Some channels are open; these receptors have bound agonist molecules. A light flash isomerizes 3(-35)% of the trans-Bis-Q molecules to their cis form, a far poorer agonist. This causes a rapid decrease of membrane conductance (phase 1), followed by a slower increase (phase 2). Phase 1 has the amplitude and wavelength dependence expected if the channel closes within 100 mus after a single bound trans-Bis-Q is isomerized, and if the photochemistry of bound Bis-Q resembles that in solution. Therefore, the receptor channel responds rapidly, and with a hundred-fold greater closing rate, after this change in the structure of a bound ligand. Phase 2 (the conductance increase) seems to represent the relaxation back toward equilibrium after phase 1, because (a) phase 2 has the same time constant (1(-5) ms) as a voltage- or concentration-jump relaxation under identical conditions; and (b) phase 2 is smaller if the flash has led to a net decrease in (trans-Bis-Q). Still slower signals follow: phase 3, a decrease of conductance (time constant 5(-10 ms); and phase 4, an equal and opposite increase (several seconds). Phase 3 is abolished by curare and does not depend on the history of the membrane voltage. We consider several mechanisms for phases 3 and 4.

Item Type:Article
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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1978 The Biophysical Society. Published by Elsevier Under an Elsevier user license. Received for publication 1 December 1977. We thank D. Williams for help with the animals, M. Walsh for help with the optics and electronics, H. W. Chang for furnishing the Bis-Q, and D. Armstrong, R. K. Clayton, B. F. Erlanger, R. E. Sheridan, and N. H. Wassermann for helpful discussion. This research was supported by a postdoctoral fellowship from the Muscular Dystrophy Association of America to M.M.N., by an Alfred P. Sloan Research Fellowship and National Institutes of Health Career Development Award (NS-272) to H.A.L., by an N.I.H. predoctoral training grant to M.E.K., and by research grants from the Muscular Dystrophy Association and the N.I.H. (NS-11756).
Funding AgencyGrant Number
Muscular Dystrophy Association of AmericaUNSPECIFIED
Alfred P. Sloan FoundationUNSPECIFIED
NIH Postdoctoral FellowshipNS-272
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC1473870
Record Number:CaltechAUTHORS:20201005-113706084
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Official Citation:M.M. Nass, H.A. Lester, M.E. Krouse, Response of acetylcholine receptors to photoisomerizations of bound agonist molecules, Biophysical Journal, Volume 24, Issue 1, 1978, Pages 135-160, ISSN 0006-3495,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105798
Deposited By: George Porter
Deposited On:05 Oct 2020 19:44
Last Modified:16 Nov 2021 18:46

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