Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 7 June 2011
Vol. 4, Issue 176, p. ra37
[DOI: 10.1126/scisignal.2001726]

RESEARCH ARTICLES

TWIK-1 Two-Pore Domain Potassium Channels Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia

Liqun Ma, Xuexin Zhang, and Haijun Chen*

Department of Biological Sciences, University at Albany, State University of New York, Albany, NY 12222, USA.

Abstract: Background potassium (K+) channels, which are normally selectively permeable to K+, maintain the cardiac resting membrane potential at around –80 mV. In subphysiological extracellular K+ concentrations ([K+]o), which occur in pathological hypokalemia, the resting membrane potential of human cardiomyocytes can depolarize to around –50 mV, whereas rat and mouse cardiomyocytes become hyperpolarized, consistent with the Nernst equation for K+. This paradoxical depolarization of cardiomyocytes in subphysiological [K+]o, which may contribute to cardiac arrhythmias, is thought to involve an inward leak sodium (Na+) current. Here, we show that human cardiac TWIK-1 (also known as K2P1) two-pore domain K+ channels change ion selectivity, becoming permeable to external Na+, and conduct inward leak Na+ currents in subphysiological [K+]o. A specific threonine residue (Thr118) within the pore selectivity sequence TxGYG was required for this altered ion selectivity. Mouse cardiomyocyte–derived HL-1 cells exhibited paradoxical depolarization with ectopic expression of TWIK-1 channels, whereas TWIK-1 knockdown in human spherical primary cardiac myocytes eliminated paradoxical depolarization. These findings indicate that ion selectivity of TWIK-1 K+ channels changes during pathological hypokalemia, elucidate a molecular basis for inward leak Na+ currents that could trigger or contribute to cardiac paradoxical depolarization in lowered [K+]o, and identify a mechanism for regulating cardiac excitability.

* To whom correspondence should be addressed. E-mail: hchen01{at}albany.edu

Citation: L. Ma, X. Zhang, H. Chen, TWIK-1 Two-Pore Domain Potassium Channels Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia. Sci. Signal. 4, ra37 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SUMOylation Silences Heterodimeric TASK Potassium Channels Containing K2P1 Subunits in Cerebellar Granule Neurons.
L. D. Plant, L. Zuniga, D. Araki, J. D. Marks, and S. A. N. Goldstein (2012)
Science Signaling 5, ra84
   Abstract »    Full Text »    PDF »
Acid-sensitive TWIK and TASK Two-pore Domain Potassium Channels Change Ion Selectivity and Become Permeable to Sodium in Extracellular Acidification.
L. Ma, X. Zhang, M. Zhou, and H. Chen (2012)
J. Biol. Chem. 287, 37145-37153
   Abstract »    Full Text »    PDF »
TWIK1, a unique background channel with variable ion selectivity.
F. C. Chatelain, D. Bichet, D. Douguet, S. Feliciangeli, S. Bendahhou, M. Reichold, R. Warth, J. Barhanin, and F. Lesage (2012)
PNAS 109, 5499-5504
   Abstract »    Full Text »    PDF »
The Inner Workings of a Dynamic Duo.
H. Poulsen and P. Nissen (2012)
Science 335, 416-417
   Abstract »    Full Text »    PDF »
Crystal Structure of the Human Two-Pore Domain Potassium Channel K2P1.
A. N. Miller and S. B. Long (2012)
Science 335, 432-436
   Abstract »    Full Text »    PDF »
K2P Potassium Channels, Mysterious and Paradoxically Exciting.
S. A. N. Goldstein (2011)
Science Signaling 4, pe35
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882