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ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes

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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.

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Funding

This work was supported by the State Key Program of National Natural Science Foundation of China (No. 81530015 to Yi-Gang Li), National Natural Science Foundation of China grant (No. 81270258 to Yi-Gang Li, Nos. 81370257, 81670414 to Yue-Peng Wang). and Shanghai City Committee of Science and Technology Research Projects (Nos. 12411951900, 13140903801, and 14441902502 to Yi-Gang Li).

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  1. Jian-Wen Hou and Wei Li contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China

    Jian-Wen Hou, Wei Li, Yu-Dong Fei, Yi-He Chen, Qian Wang, Yue-Peng Wang & Yi-Gang Li

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  1. Jian-Wen Hou
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Correspondence to Yue-Peng Wang or Yi-Gang Li.

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Hou, JW., Li, W., Fei, YD. et al. ICaL and Ito mediate rate-dependent repolarization in rabbit atrial myocytes. J Physiol Biochem 74, 57–67 (2018). https://doi.org/10.1007/s13105-017-0603-z

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