TY - JOUR
T1 - Ablation of a Ca2+-activated K+ channel (SK2 channel) results in action potential prolongation in atrial myocytes and atrial fibrillation
AU - Li, Ning
AU - Timofeyev, Valeriy
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
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
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U2 - 10.1113/jphysiol.2008.167718
DO - 10.1113/jphysiol.2008.167718
M3 - Article
C2 - 19139040
AN - SCOPUS:61649127297
SN - 0022-3751
VL - 587
SP - 1087
EP - 1100
JO - Journal of Physiology
JF - Journal of Physiology
IS - 5
ER -