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Activation of acetylcholine receptor channels by covalently bound agonists in cultured rat myoballs

Chabala, Lee D. and Lester, Henry A. (1986) Activation of acetylcholine receptor channels by covalently bound agonists in cultured rat myoballs. Journal of Physiology, 379 (1). pp. 83-108. ISSN 0022-3751. PMCID PMC1182886. doi:10.1113/jphysiol.1986.sp016242.

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Kinetic and equilibrium aspects of receptor activation by two irreversibly bound ('tethered') agonists, QBr and bromoacetylcholine (BrACh), were examined in cultured embryonic rat muscle. Myoballs were treated with dithiothretitol (2 mM), washed, exposed to BrACh or QBr, and then washed again. Voltage‐clamp recordings were made both in the whole‐cell mode and with excised outside‐out patches at 15 degrees C. Whole‐cell voltage‐jump relaxations resembled those observed with reversibly bound agonists. The relaxation time constants were 5 ms for tethered QBr and 10 ms for tethered BrACh (‐100 mV, 15 degrees C). At more positive membrane potentials, the relaxation rate constants increased and the conductance decreased. Whole‐cell light‐flash relaxations with tethered QBr were also studied. The conductance was increased and decreased, respectively, by cis→trans and trans→cis photoisomerizations. The relaxation time constants equalled those for voltage jumps. The functional stoicheiometry of tethered QBr was investigated by studying the relaxations in response to light flashes that produced known changes in the mole fractions of the two isomers. It is concluded that the open state of each receptor channel is controlled by the isomeric state of a single tethered QBr molecule. In single‐channel recordings, tethered agonists opened channels with the same conductance as reversibly bound agonists (30 pS at 15 degrees C and ‐100 mV). More than 80% of the conductance was contributed by a population of openings with an average burst duration (lifetime) of 5 ms for QBr and 10 ms for BrACh. Thus the single‐channel and macroscopic currents seem to be dominated by the same type of channel; these are presumably monoliganded receptors. About 30% of the openings belonged to a population with an average lifetime of about 0.5 ms. This population contributed less than 5% of the conductance. There were also more long openings (greater than 50 ms) than expected from a simple exponential distribution. A few patches from BrACh‐treated cells showed openings with a conductance of 45 pS (‐100 mV) and an average duration of approximately 2 ms. These data allow one to assess whether the agonist‐receptor binding step plays a role in generating the brief openings. The main population of openings (burst durations 5 ms with QBr and 10 ms with BrACh) seem to be contributed by monoliganded receptors. One can therefore rule out the hypothesis that the brief channels arise exclusively from mono‐ and biliganded receptors, respectively.

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Lester, Henry A.0000-0002-5470-5255
Additional Information:© 1986 The Physiological Society. (Received 21 May 1985) We thank C. Ifune for participating in some of the experiments, Dr M. A. Raftery for supplying BrACh, and Drs N. H. Wassermann and B. F. Erlanger for supplying QBr. This research was supported by a fellowship from the Muscular Dystrophy Association of America to L. D. C. and by a grant from the NIH (NS-11756).
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Muscular Dystrophy Association of AmericaUNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC1182886
Record Number:CaltechAUTHORS:20201012-152226105
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Official Citation:Chabala, L D, Lester, H A, (1986), Activation of acetylcholine receptor channels by covalently bound agonists in cultured rat myoballs. The Journal of Physiology, 379 doi: 10.1113/jphysiol.1986.sp016242.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105993
Deposited By: George Porter
Deposited On:13 Oct 2020 14:13
Last Modified:16 Nov 2021 18:48

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