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TRPV1 channels regulate the automaticity of embryonic stem cell‐derived cardiomyocytes through stimulating the Na + /Ca 2+ exchanger current
Author(s) -
Zhao Rui,
Liu Xianji,
Qi Zenghua,
Yao Xiaoqiang,
Tsang Suk Ying
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30369
Subject(s) - trpv1 , chemistry , calcium , endoplasmic reticulum , calcium in biology , electrophysiology , biophysics , capsazepine , calcium imaging , voltage dependent calcium channel , sodium calcium exchanger , microbiology and biotechnology , transient receptor potential channel , biochemistry , neuroscience , receptor , biology , organic chemistry
Calcium controls the excitation–contraction coupling in cardiomyocytes. Embryonic stem cell‐derived cardiomyocytes (ESC‐CMs) are an important cardiomyocyte source for regenerative medicine and drug screening. Transient receptor potential vanilloid 1 (TRPV1) channels are nonselective cation channels that permeate sodium and calcium. This study aimed to investigate whether TRPV1 channels regulate the electrophysiological characteristics of ESC‐CMs. If yes, what is the mechanism behind? By immunostaining and subcellular fractionation, followed by western blotting, TRPV1 was found to locate intracellularly. The staining pattern of TRPV1 was found to largely overlap with that of the sarco/endoplasmic reticulum Ca 2+ ‐ATPase, the sarcoplasmic reticulum (SR) marker. By electrophysiology and calcium imaging, pharmacological blocker of TRPV1 and the molecular tool TRPV1β (which could functionally knockdown TRPV1) were found to decrease the rate and diastolic depolarization slope of spontaneous action potentials, and the amplitude and frequency of global calcium transients. By calcium imaging, in the absence of external calcium, TRPV1‐specific opener increased intracellular calcium; this increase was abolished by preincubation with caffeine, which could deplete SR calcium store. The results suggest that TRPV1 controls calcium release from the SR. By electrophysiology, TRPV1 blockade and functional knockdown of TRPV1 decreased the Na + /Ca2 + exchanger (NCX) currents from both the forward and reverse modes, suggesting that sodium and calcium through TRPV1 stimulate the NCX activity. Our novel findings suggest that TRPV1 activity is important for regulating the spontaneous activity of ESC‐CMs and reveal a novel interplay between TRPV1 and NCX in regulating the physiological functions of ESC‐CMs.