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J. Biol. Chem., Vol. 276, Issue 46, 43166-43174, November 16, 2001
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From the Centro de Estudios Científicos, Av. Arturo Prat
514, Casilla 1469, Valdivia, Chile
The molecular identity of K+
channels involved in Ehrlich cell volume regulation is unknown. A
background K+ conductance is activated by cell swelling and
is also modulated by extracellular pH. These characteristics are most
similar to those of newly emerging TASK (TWIK-related
acid-sensitive K+ channels)-type of two pore-domain
K+ channels. mTASK-2, but not TASK-1 or -3, is present in
Ehrlich cells and mouse kidney tissue from where the full coding
sequences were obtained. Heterologous expression of mTASK-2 cDNA in
HEK-293 cells generated K+ currents in the absence
intracellular Ca2+. Exposure to hypotonicity enhanced
mTASK-2 currents and osmotic cell shrinkage led to inhibition. This
occurred without altering voltage dependence and with only slight
decrease in pKa in hypotonicity but no change in
hypertonicity. Replacement with other cations yields a
permselectivity sequence for mTASK-2 of K+ > Rb+
Modulation of the Two-pore Domain Acid-sensitive
K+ Channel TASK-2 (KCNK5) by Changes in Cell Volume*
,
Cs+ > NH
Li+, similar to that for the native conductance
(IK, vol). Clofilium, a quaternary ammonium
blocker of IK, vol, blocked the
mTASK-2-mediated K+ current with an IC50 of 25 µM. The presence of mTASK-2 in Ehrlich cells, its
functional similarities with IK, vol, and its modulation by changes in cell volume suggest that this two-pore domain
K+ channel participates in the regulatory volume decrease phenomenon.
*
This work was supported in part by Fondecyt and an Equipment
Grant from Fundación Andes and by institutional support to the Centro de Estudios Científicos from a group of Chilean private companies (CODELCO, DIMACOFI, Empresas CMPC, MASISA S.A., and Telefónica del Sur).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.
To whom correspondence should be addressed: Tel.: 56-63-234500;
Fax: 56-63-234515; E-mail: miniemeyer@cecs.cl.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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