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GENERAL ARTICLES

Patch-Clamp Analysis of Anesthetic Interactions with Recombinant SK2 Subtype Neuronal Calcium-Activated Potassium Channels

Department of Anesthesia and Critical Care, University of Chicago, Chicago, Illinois

Address correspondence and reprint requests to Dr. Khaled M. Houamed, Department of Anesthesia and Critical Care, The University of Chicago Medical Center, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637. Address e-mail to khouamed{at}midway.uchicago.edu

Small conductance calcium-activated potassium channels (SK) mediate spike frequency adaptation and underlie the slow afterhyperpolarization in central neurons. We tested the actions of several anesthetics on the SK2 subtype of recombinant SK channels, cloned from rat brain and functionally expressed in a mammalian cell line. Butanol, ethanol, ketamine, lidocaine, and methohexital blocked recombinant SK2 channel currents, measured in the whole-cell patch clamp recording mode. The block was reversible, dose-dependent, and of variable efficacy. The inhaled anesthetics chloroform, desflurane, enflurane, halothane, isoflurane, and sevoflurane produced little or no block when applied at 1 minimum alveolar anesthetic concentration; varying degrees of modulation were observed at very large concentrations (10 minimum alveolar concentration). The extent of block by inhaled anesthetics did not appear to depend on concentration or membrane voltage.

Implications: We describe differential effects of anesthetics on cloned small conductance calcium-activated potassium channels from brain that may play a role in generating the effects or side effects of anesthetics.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999