Open AccessArrhythmogenesis in heart cells involves reverse E–C coupling and reverse electrotonic conduction along T-tubules
Author(s) -
Takeshi Shioya
Publication year - 2021
Publication title -
the journal of general physiology/the journal of general physiology
Language(s) - English
Resource type - Journals
eISSN - 1540-7748
pISSN - 0022-1295
DOI - 10.1085/jgp.2021ecc29
Subject(s) - depolarization , afterdepolarization , biophysics , coupling (piping) , membrane potential , extracellular , intracellular , endoplasmic reticulum , electrophysiology , biology , microbiology and biotechnology , chemistry , neuroscience , repolarization , materials science , metallurgy
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.