title: Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation.
abstract: Small conductance Ca(2+)-activated K(+) channels (SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(2+)(i)) 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. Moreover, 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.
authors.affiliation: Division of Cardiovascular Medicine, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Valeriy
authors.initials: V
authors.lastname: Timofeyev
authors.forename: Dipika
authors.initials: D
authors.lastname: Tuteja
authors.forename: Danyan
authors.initials: D
authors.lastname: Xu
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Anil
authors.initials: A
authors.lastname: Singapuri
authors.forename: Trevine R
authors.initials: TR
authors.lastname: Albert
authors.forename: Amutha V
authors.initials: AV
authors.lastname: Rajagopal
authors.forename: Chris T
authors.initials: CT
authors.lastname: Bond
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
authors.forename: John
authors.initials: J
authors.lastname: Adelman
authors.forename: Nipavan
authors.initials: N
authors.lastname: Chiamvimonvat
mesh_terms: D000200:Action Potentials / Q000235:genetics*; D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000473:pathology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000172:deficiency* / Q000235:genetics*
chemical_list: C496898:Kcnn2 protein, mouse; D051640:Small-Conductance Calcium-Activated Potassium Channels