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ANESTHETIC PHARMACOLOGY

Species-Specific Differences in Response to Anesthetics and Other Modulators by the K_2P Channel TRESK

Bharat Keshavaprasad, MD^*, Canhui Liu, PhD^*, John D. Au, MD^*, Christoph H. Kindler, MD, Joseph F. Cotten, MD PhD^*, and C. Spencer Yost, MD^*

*Department of Anesthesia and Perioperative Care, University of California San Francisco, San Francisco, California; Department of Anesthesia, University Hospital Basel, Basel, Switzerland

Address correspondence and reprint requests to C. Spencer Yost, MD, Department of Anesthesia and Perioperative Care, 513 Parnassus Ave., Room S-261, Box 0542, San Francisco, CA 94143. Address e-mail to yosts{at}anesthesia.ucsf.edu.

TRESK (TWIK-related spinal cord K⁺ channel) is the most recently characterized member of the tandem-pore domain potassium channel (K_2P) family. Human TRESK is potently activated by halothane, isoflurane, sevoflurane, and desflurane, making it the most sensitive volatile anesthetic-activated K_2P channel yet described. Herein, we compare the anesthetic sensitivity and pharmacologic modulation of rodent versions of TRESK to their human orthologue. Currents passed by mouse and rat TRESK were enhanced by isoflurane at clinical concentrations but with significantly lower efficacy than human TRESK. Unlike human TRESK, the rodent TRESKs are strongly inhibited by acidic extracellular pH in the physiologic range. Zinc inhibited currents passed by both rodent TRESK in the low micromolar range but was without effect on human TRESK. Enantiomers of isoflurane that have stereoselective anesthetic potency in vivo produced stereospecific enhancement of the rodent TRESKs in vitro. Amide local anesthetics inhibited the rodent TRESKs at almost 10-fold smaller concentrations than that which inhibit human TRESK. These results identified interspecies differences and similarities in the pharmacology of TRESK. Further characterization of TRESK expression patterns is needed to understand their role in anesthetic mechanisms.

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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