TRPV1 channels regulate the automaticity of embryonic stem cell-derived cardiomyocytes through stimulating the Na + /Ca 2+ exchanger current.

Autor: Zhao R; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China., Liu X; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China., Qi Z; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China., Yao X; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China., Tsang SY; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong, China.; Key Laboratory for Regenerative Medicine, Ministry of Education, The Chinese University of Hong Kong, Hong Kong, China.
Jazyk: angličtina
Zdroj: Journal of cellular physiology [J Cell Physiol] 2021 Oct; Vol. 236 (10), pp. 6806-6823. Date of Electronic Publication: 2021 Mar 30.
DOI: 10.1002/jcp.30369
Abstrakt: 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.
(© 2021 Wiley Periodicals LLC.)
Databáze: MEDLINE
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