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

Editor's Summary

Losing Selectivity
When the serum potassium drops to very low concentrations (pathological hypokalemia), the resting membrane potential of human cardiomyocytes can depolarize, rather than hyperpolarizing as would be predicted by the Nernst equation. This paradoxical depolarization, which is thought to be mediated by an inward sodium current, may contribute to the abnormalities of cardiac rhythm that can occur under conditions of pathological hypokalemia—or even cardiac arrest. Here, Ma et al. show that the ion selectivity of TWIK-1 channels, members of a class of potassium-selective ion channels that help maintain the resting membrane potential, changes at subphysiological extracellular potassium concentrations, so that they become permeable to sodium as well. Ectopic expression of TWIK-1 channels in a mouse cardiomyocyte cell line led to paradoxical depolarization in the presence of low extracellular potassium, whereas loss of TWIK-1 in cultured human cardiomyocytes abolished their paradoxical depolarization. Thus, by losing their selectivity for potassium and becoming permeable to sodium, TWIK-1 channels may contribute to cardiac paradoxical depolarization in pathological hypokalemia.

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