Mechanism of volatile anesthetic action on ion channels.
Single channel recording techniques have been used to study effects of halothane and isoflurane on the properties of nicotinic channels activated by 250 nM acetylcholine in cell-attached patches of BC3H1 mouse tumor cells grown in culture. Halothane and isoflurane were diluted in air and delivered as vapors in the atmosphere above the cells. Both halothane and isoflurane shortened the duration of individual opening events and caused openings to appear grouped together in bursts. The slower time constant of channel open-time distributions was decreased 50% by approximately 0.25% isoflurane (0.12 mM) or 0.30% halothane (0.15 mM) at room temperature. Total open time per burst was also decreased by each agent, an effect that is not consistent with a sequential channel blocking model. Effects of halothane and isoflurane can be explained by a sequential blocking model only if anesthetics also enhance the rate at which open channels normally close. Alternatively, results are also consistent with a cyclic blocking model in which blocked channels may close directly without having to pass back through the open state.
Wachtel
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Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246.
Wegrzynowicz
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D006221:Halothane / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D008954:Models, Biological
D007473:Ion Channels; D007530:Isoflurane; D000109:Acetylcholine; D006221:Halothane