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J. Biol. Chem., Vol. 275, Issue 22, 16969-16978, June 2, 2000
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From the Section of Developmental Biology and Biophysics,
Departments of Pediatrics and Cellular and Molecular Physiology, Boyer
Center for Molecular Medicine, Yale University School of Medicine,
New Haven, Connecticut 06536
Potassium leak conductances were recently
revealed to exist as independent molecular entities. Here, the genomic
structure, cardiac localization, and biophysical properties of a murine
example are considered. Kcnk3 subunits have two pore-forming P domains and unique functional attributes. At steady state, Kcnk3 channels behave like open, potassium-selective, transmembrane holes that are
inhibited by physiological levels of proton. With voltage steps, Kcnk3
channels open and close in two phases, one appears to be immediate and
one is time-dependent (
Proton Block and Voltage Gating Are
Potassium-dependent in the Cardiac Leak Channel
Kcnk3*
,
= ~5 ms). Both proton block and gating are potassium-sensitive; this produces an anomalous increase in outward flux as external potassium levels rise because of
decreased proton block. Single Kcnk3 channels open across the physiological voltage range; hence they are "leak" conductances; however, they open only briefly and rarely even after exposure to
agents that activate other potassium channels.
*
This work was supported by a grant from the National
Institutes of Health (to S. A. N. G.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported in-part by grants from the National Institutes of
Health, the Yale University Children's Health Research Center, and the
March of Dimes Birth Defects Foundation.
§
To whom correspondence should be addressed: 295 Congress Ave., New
Haven, CT 06536. Tel.: 203-737-2214; Fax: 203-737-2290; E-mail:
steve.goldstein@yale.edu.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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