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Published October 1978 | public
Journal Article

Response of acetylcholine receptors to photoisomerizations of bound agonist molecules

Abstract

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.

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).

Additional details

Created:
August 19, 2023
Modified:
October 20, 2023