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Molecular Pharmacology, Vol 16, 1075-1083, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

The Mean Conductance and Open-Time of the Acetylcholine Receptor Channels Can Be Independently Modified by Some Anesthetic and Convulsant Ethers

EMMANUEL M. LANDAU 1, JACOB RICHTER 1, and SASSON COHEN 1

1 Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

The effects of two anesthetic ethers, methoxyflurane and diethyl ether (ether), and one convulsant ether, fluothyl, were examined on miniature end-plate currents and on end-plate current fluctuations at the frog neuromuscular junction. Either methoxyflurane or fluothyl was found to reduce the amplitude and the half-decay time of the miniature end-plate currents. When the concentration of methoxyflurane was raised from 10-4 to 5.10-4 M its effect on the miniature end-plate current amplitude was increased but that on the half-decay time remained unaltered. The effect of ether on the miniature end-plate current was dose-dependent: at 10-3 M it reduced the half-decay time without affecting the amplitude, whereas at 10-2 M it increased the half-decay time and decreased the amplitude. Analysis of end-plate current fluctuations revealed that the effects of methoxyflurane (5.10-4 M) and ether (10-2 M) on the mean conductance and open-time of the acetylcholine receptor channels were comparable to their effects on the amplitude and the half-decay time of the miniature end-plate current. It is concluded that the effect of such structurally "non-specific" drugs comprises a combination of discrete and distinguishable events which are specific and dose-dependent for each of the agents used.

Note:
ACKNOWLEDGMENT We are grateful to Mrs. Solange Akselrod for helping us with the computer programming, Professor J. Goldstein for permitting us to use the computer, Dr. A. Goldschmid for supplying us with fluothyl, and Professor S. Gitter for his interest and encouragement. This work is part of a Ph.D. thesis submitted by J.R. to the Tel-Aviv University. The research was partly supported by a grant from U.S-Israel Binational Science Foundation, (BSF), Jerusalem.

Submitted on October 10, 1978
Accepted on July 24, 1979






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