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Physostigmine block of ion channels activated by acetylcholine in BC3H1 cells

RE Wachtel

Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246.

Single-channel recording techniques have been used to study the effects of physostigmine on the kinetics of ion channels activated by acetylcholine in BC3H1 mouse tumor cells grown in culture. Physostigmine reduced mean channel open time, with 50% reduction occurring at about 7 microM physostigmine. Although openings did not appear to occur in bursts, channel closed-time distributions exhibited a new component 7-8 msec in duration. The area of this component, but not its time constant, increased with higher concentrations of physostigmine. Results are consistent with a simple sequential channel- blocking model in which the new closed-time component represents a blocked state of the channel. Membrane hyperpolarization increased the potency of physostigmine in reducing channel open time and also prolonged the duration of the blocked state. The voltage dependence of physostigmine block was unexpected, because physostigmine is uncharged at physiological pH.

Volume 44, Issue 5, pp. 1051-1055, 11/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics