Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation

Ning Li, Valeriy Timofeyev, Dipika Tuteja, Danyan Xu, Ling Lu, Qian Zhang, Zhao Zhang, Anil Singapuri, Trevine R. Albert, Amutha V. Rajagopal, Chris T. Bond, Muthu Periasamy, John Adelman, Nipavan Chiamvimonvat

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Abstract

Small conductance Ca2+-activated K+ channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca2+ (Cai2+) with membrane potential. We have recently reported the functional existence of SK2 channels in human and mouse cardiac myocytes. Moreover, we have found that the channel is predominantly expressed in atria compared to the ventricular myocytes. We hypothesize that knockout of SK2 channels may be sufficient to disrupt the intricate balance of the inward and outward currents during repolarization in atrial myocytes. We further predict that knockout of SK2 channels may predispose the atria to tachy-arrhythmias due to the fact that the late phase of the cardiac action potential is highly susceptible to aberrant excitation. We take advantage of a mouse model with genetic knockout of the SK2 channel gene. In vivo and in vitro electrophysiological studies were performed to probe the functional roles of SK2 channels in the heart. Whole-cell patch-clamp techniques show a significant prolongation of the action potential duration prominently in late cardiac repolarization in atrial myocytes from the heterozygous and homozygous null mutant animals. Morover, in vivo electrophysiological recordings show inducible atrial fibrillation in the null mutant mice but not wild-type animals. No ventricular arrhythmias are detected in the null mutant mice or wild-type animals. In summary, our data support the important functional roles of SK2 channels in cardiac repolarization in atrial myocytes. Genetic knockout of the SK2 channels results in the delay in cardiac repolarization and atrial arrhythmias.

Original languageEnglish (US)
Pages (from-to)1087-1100
Number of pages14
JournalJournal of Physiology
Volume587
Issue number5
DOIs
StatePublished - 2009

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Atrial Fibrillation
Muscle Cells
Action Potentials
Cardiac Arrhythmias
Wild Animals
Intracellular Membranes
Genetic Models
Patch-Clamp Techniques
Cardiac Myocytes
Membrane Potentials
Genes

ASJC Scopus subject areas

  • Physiology
  • Medicine(all)

Cite this

Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation. / Li, Ning; Timofeyev, Valeriy; Tuteja, Dipika; Xu, Danyan; Lu, Ling; Zhang, Qian; Zhang, Zhao; Singapuri, Anil; Albert, Trevine R.; Rajagopal, Amutha V.; Bond, Chris T.; Periasamy, Muthu; Adelman, John; Chiamvimonvat, Nipavan.

In: Journal of Physiology, Vol. 587, No. 5, 2009, p. 1087-1100.

Research output: Contribution to journalArticle

Li, N, Timofeyev, V, Tuteja, D, Xu, D, Lu, L, Zhang, Q, Zhang, Z, Singapuri, A, Albert, TR, Rajagopal, AV, Bond, CT, Periasamy, M, Adelman, J & Chiamvimonvat, N 2009, 'Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation', Journal of Physiology, vol. 587, no. 5, pp. 1087-1100. https://doi.org/10.1113/jphysiol.2008.167718
Li, Ning ; Timofeyev, Valeriy ; Tuteja, Dipika ; Xu, Danyan ; Lu, Ling ; Zhang, Qian ; Zhang, Zhao ; Singapuri, Anil ; Albert, Trevine R. ; Rajagopal, Amutha V. ; Bond, Chris T. ; Periasamy, Muthu ; Adelman, John ; Chiamvimonvat, Nipavan. / Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation. In: Journal of Physiology. 2009 ; Vol. 587, No. 5. pp. 1087-1100.
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AU - Tuteja, Dipika

AU - Xu, Danyan

AU - Lu, Ling

AU - Zhang, Qian

AU - Zhang, Zhao

AU - Singapuri, Anil

AU - Albert, Trevine R.

AU - Rajagopal, Amutha V.

AU - Bond, Chris T.

AU - Periasamy, Muthu

AU - Adelman, John

AU - Chiamvimonvat, Nipavan

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