In-vivo characterisation and mutation screening of the cardiac two-pore potassium channel, TWIK-1

Martin, I.; Christensen, Alex Hørby; Soka, Magdalena; Fatkin, Diane

doi:10.1016/j.hlc.2014.07.036

Cited by 1 publication

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“…12,20 Missense mutations of K2P1 channels may be associated with familial atrial fibrillation. 21 Recent studies showed that K2P1 channels have a highly conserved role in the cardiac function of zebrafish. 22 Previously, we discovered that in lowered [K + ] o that occurs under hypokalemia, K2P1 channels dynamically change ion selectivity, become nonselective leak cation channels, and conduct inward depolarizing leak cation (mainly Na + ) currents.…”

Section: Introductionmentioning

confidence: 99%

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K2P1 leak cation channels contribute to ventricular ectopic beats and sudden death under hypokalemia

et al. 2022

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Hypokalemia causes ectopic heartbeats, but the mechanisms underlying such cardiac arrhythmias are not understood. In reduced serum K + concentrations that occur under hypokalemia, K2P1 two-pore domain K + channels change ion selectivity and switch to conduct inward leak cation currents, which cause aberrant depolarization of resting potential and induce spontaneous action potential of human cardiomyocytes. K2P1 is expressed in the human heart but not in mouse hearts. We test the hypothesis that K2P1 leak cation channels contribute to ectopic heartbeats under hypokalemia, by analysis of transgenic mice, which conditionally express induced K2P1 specifically in hearts, mimicking K2P1 channels in the human heart. Conditional expression of induced K2P1 specifically in the heart of hypokalemic mice results in multiple types of ventricular ectopic beats including single and multiple ventricular premature beats as well as ventricular tachycardia and causes sudden death. In isolated mouse hearts that express induced K2P1, sustained ventricular fibrillation occurs rapidly after perfusion with low K + concentration solutions that mimic hypokalemic conditions. These observed phenotypes occur rarely in control mice or in the hearts

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Section: Introductionmentioning

confidence: 99%

“…K2P1 proteins are detected in the human atrium and ventricle 12,20 . Missense mutations of K2P1 channels may be associated with familial atrial fibrillation 21 . Recent studies showed that K2P1 channels have a highly conserved role in the cardiac function of zebrafish 22 .…”

Section: Introductionmentioning

confidence: 99%