TRPC3 regulates the automaticity of embryonic stem cell-derived cardiomyocytes.

Autor: Qi Z; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong., Wong CK; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong., Suen CH; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong., Wang J; School of Life Sciences, South China Normal University, Guangzhou, PR China., Long C; School of Life Sciences, South China Normal University, Guangzhou, PR China., Sauer H; Department of Physiology, Justus Liebig University Giessen, Germany., Yao X; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong., Tsang SY; School of Life Sciences, The Chinese University of Hong Kong, Hong Kong; Key Laboratory for Regenerative Medicine, Ministry of Education, The Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Agrobiotechnology, The Chinese University of Hong Kong, Hong Kong; Centre for Novel Biomaterials, The Chinese University of Hong Kong, Hong Kong. Electronic address: fayetsang@cuhk.edu.hk.
Jazyk: angličtina
Zdroj: International journal of cardiology [Int J Cardiol] 2016 Jan 15; Vol. 203, pp. 169-81. Date of Electronic Publication: 2015 Oct 09.
DOI: 10.1016/j.ijcard.2015.10.018
Abstrakt: Background: Cardiac pacemaking is a complex phenomenon that is not completely understood. Canonical transient receptor potential isoform 3 (TRPC3) channel is a cation channel that permeates both Ca(2+) and Na(+). TRPC3 was previously found to express in adult cardiomyocytes. However, its role in cardiac pacemaking is unexplored. Here we used mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) to investigate whether TRPC3 regulates the spontaneous automaticity and the underlying mechanism involved.
Methods and Results: Immunocytochemistry results showed that TRPC3 is expressed at the T-tubules of mESC-CMs. Whole-cell patch clamping showed that single mESC-CMs contain TRPC3 current. Confocal Ca(2+) imaging showed that the TRPC3-specific blocker Pyr3 decreased Ca(2+) transients and local Ca(2+) release (LCR) of mESC-CMs. Combined current and voltage clamp recordings from the same cell showed that reducing the TRPC3 current, either by Pyr3 or a dominant negative (loss-of-function) construct of TRPC3, decreased the pacemaker activity of mESC-CMs as reflected by a decrease in action potential rate, a depolarized maximum diastolic potential and a decrease in slope of phase 4 diastolic depolarization. Furthermore, decreasing the TRPC3 current diminished, while increasing the TRPC3 current augmented the sodium-calcium exchanger (NCX) current in mESC-CMs. Lastly, decrease in TRPC3 current decreased the phosphorylation of ryanodine receptor isoform 2 at Ser2809 and phospholamban at Thr17.
Conclusions: TRPC3 positively regulates diastolic depolarization of spontaneous action potential by increasing LCR and NCX current and therefore is an important determinant in pacemaking of mESC-CMs.
(Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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