Early afterdepolarization (EAD) is an aberrant cardiac afterpotential that underlies the development of life-threatening ventricular arrhythmias. It is believed that the development of EAD is caused by the reactivation of L-type Ca2+ current during the period of the action potential plateau; however, the cellular mechanisms that underlie the development of EAD is still controversial. One favorable alternative is the depolarizing reverse-mode operation of the Na+/Ca2+ exchanger, which is activated by aberrant Ca2+ release from the sarcoplasmic reticulum in the process of reverse E–C coupling. Since EADs develop preferentially in damaged heart cells with abnormal Ca2+-signaling, here I studied the causal link between the development of EADs and aberrant intracellular Ca2+ level ([Ca2+]i) dynamics in mouse heart cells using the whole-cell clamp technique. My results show (1) the generation of EADs was preceded by the development of depolarizing membrane potential (Vm) fluctuation, (2) the depolarizing Vm fluctuation is associated with [Ca2+]i elevation, suggesting an involvement of reverse E–C coupling via the Na+/Ca2+ exchanger, and (3) that extending the T-tubules’ length constant by decreasing the extracellular K+ level facilitated the development of the Vm fluctuation and EADs. Taken together, I conclude that EADs are caused by the depolarizing Vm fluctuation, which is induced locally in the T-tubule membrane by aberrant [Ca2+]i elevation and is conducted back electrotonically along the T-tubules.
Meeting Abstract|
E–C Coupling Meeting 2021|
November 12 2021
Arrhythmogenesis in heart cells involves reverse E–C coupling and reverse electrotonic conduction along T-tubules: Calcium Signaling and Excitation–Contraction in Cardiac, Skeletal and Smooth Muscle
Takao Shioya
Takao Shioya
1Department of Physiology, Faculty of Medicine, Saga University, Saga, Japan
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Takao Shioya
1Department of Physiology, Faculty of Medicine, Saga University, Saga, Japan
Online ISSN: 1540-7748
Print ISSN: 0022-1295
© 2021 Shioya
2021
This article is available under a Creative Commons License (Attribution–Noncommercial–Share
Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Gen Physiol (2022) 154 (9): e2021ecc29.
Citation
Takao Shioya; Arrhythmogenesis in heart cells involves reverse E–C coupling and reverse electrotonic conduction along T-tubules: Calcium Signaling and Excitation–Contraction in Cardiac, Skeletal and Smooth Muscle. J Gen Physiol 5 September 2022; 154 (9): e2021ecc29. doi: https://doi.org/10.1085/jgp.2021ecc29
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