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Excitable channel currents and gating times in the presence of anticonvulsants ethosuximide and valproate

JF Fohlmeister, WJ Adelman and JJ Brennan

The effects of the anticonvulsants ethosuximide and valproate on the excitable Na and K channels of the squid giant axon are evaluated and compared. The drugs are highly specific in their effects on channel gating and ion permeability with regard to the membrane side of application. Both drugs when applied internally affect Na activation gating in ways that lead to the conclusion that they do not act as channel blockers. However, external ethosuximide is clearly a voltage- independent Na channel blocker with no effect on channel gating. On the K channel, ethosuximide appears to have a mixed action affecting both gating and the ion flux through open channels. However, valproate slows K channel gating without effect on the flux through open channels. The dose-response curve of the effects has a shape similar to that for ethanol. The implications for paroxysmal discharge and synchronous impulse generation are discussed in a preliminary way.

Volume 230, Issue 1, pp. 75-81, 07/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics




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