I CaL and I to mediate rate-dependent repolarization in rabbit atrial myocytes
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ORIGINAL ARTICLE
ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes Jian-Wen Hou 1 & Wei Li 1 & Yu-Dong Fei 1 & Yi-He Chen 1 & Qian Wang 1 & Yue-Peng Wang 1 & Yi-Gang Li 1 Received: 21 June 2017 / Accepted: 4 December 2017 # University of Navarra 2017
Abstract Rate-dependent repolarization (RDR) of action potential (AP) in cardiomyocyte plays a critical role in the genesis of arrhythmias and RDR in atrium has been linked with atrial fibrillation. However, detailed studies focusing on the role of RDR in rabbit atrium are scant. In this study, atrial cells were isolated from rabbit heart and rate-dependent property was explored in single atrial cell to elucidate the underlying mechanism. Our results indicated that rate-dependent prolongation was evident at the action potential duration at 20% (APD20) and 50% (APD50) repolarization but not at 90% repolarization (APD90) under control condition. Using transient outward potassium current (Ito) inhibitor 4-Aminopyridine (4-AP, 2 mM) effectively eliminated the changes in APD20 and APD50, and unmasked the rate-dependent reduction of APD90 which could be diminished by further adding L-type calcium current (ICaL) inhibitor nifedipine (30 μM). However, using the selective late sodium current (INaL) inhibitor GS-458967 (GS967, 1 μM) caused minimal effect on APD90 of atrial cells both in the absence and presence of 4-AP. In consistence with results from APs, Ito and ICaL displayed significant rate-dependent reduction because of their slow reactivation kinetics. In addition, the magnitude of INaL in rabbit atrium was so small that its rate-dependent changes were negligible. In conclusion, our study demonstrated that Ito and ICaL mediate RDR of AP in rabbit atrium, while minimal effect of INaL was seen. Keywords Atrial myocytes . Late sodium current . L-type calcium current . Rate-dependent repolarization . Transient outward potassium current
Introduction The duration and morphology of the action potential (AP) in cardiomyocyte change dramatically in response to changes in heart rates; this phenomenon is known as rate-dependent repolarization (RDR) of AP. Several ionic channels have been reported to contribute to RDR in cardiomyocytes, including the transient outward potassium current (Ito) [3], L-type calcium current (ICaL) [16], and the rapid and slow component of inward rectifier potassium current (Ikr, Iks) [13]. In ventricle, larger RDR property across the ventricular wall has been
Jian-Wen Hou and Wei Li contributed equally to this work. * Yue-Peng Wang [email protected] * Yi-Gang Li [email protected] 1
Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai 200092, China
linked with greater transmural dispersion of repolarization and stronger reverse-use dependence of Ikr blocker [11, 13, 25], which may increase the incidence of reentrant arrhythmias and Torsades de pointes [20]. Meanwhile, RDR of atrial AP has been proved to be involved in the occurrence of reentr
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