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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).

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