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The Journal of Neuroscience, February 1, 1998, 18(3):868-877
An Open Rectifier Potassium Channel with Two Pore Domains in Tandem Cloned from Rat Cerebellum
Dmitri Leonoudakis1, Andrew T. Gray1, Bruce D. Winegar1, Christoph H. Kindler1, Masato Harada1, Donald M. Taylor1, Raymond A. Chavez2, John R. Forsayeth2, and C. Spencer Yost1 1 Department of Anesthesia, University of California San Francisco, San Francisco, California 94143-0542, and 2 Neurex Corporation, Menlo Park, California 94025
Tandem pore domain K+ channels represent a new family of ion channels involved in the control of background membrane conductances. We report the structural and functional properties of a TWIK-related acid-sensitive K+ channel (rTASK), a new member of this family cloned from rat cerebellum. The salient features of the primary amino acid sequence include four putative transmembrane domains and, unlike other cloned tandem pore domain channels, a PDZ (postsynaptic density protein, disk-large, zo-1) binding sequence at the C terminal. rTASK has distant overall homology to a putative Caenorhabditis elegans K+ channel and to the mammalian clones TREK-1 and TWIK-1. rTASK expression is most abundant in rat heart, lung, and brain. When exogenously expressed in Xenopus oocytes, rTASK currents activate instantaneously, are noninactivating, and are not gated by voltage. Because rTASK currents satisfy the Goldman-Hodgkin-Katz current equation for an open channel, rTASK can be classified an open rectifier. Activation of protein kinase A produces inhibition of rTASK, whereas activation of protein kinase C has no effect. rTASK currents were inhibited by extracellular acidity. rTASK currents also were inhibited by Zn2+ (IC50 = 175 µM), the local anesthetic bupivacaine (IC50 = 68 µM), and the anti-convulsant phenytoin (~50% inhibition at 200 µM). By demonstrating open rectification and open probability independent of voltage, we have established that rTASK is a baseline potassium channel.
Key words: potassium channel; open rectifier; local anesthetics; pH; cloning; cerebellum; Xenopus oocyte; baseline channel
Copyright © 1998 Society for Neuroscience 0270-6474/98/183868-10$05.00/0
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