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Myocardial TRPC6-mediated Zn influx induces beneficial positive inotropy through β-adrenoceptors

Nature Communications, ISSN: 2041-1723, Vol: 13, Issue: 1, Page: 6374
2022
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Study Results from National Institutes of Natural Sciences Broaden Understanding of Science (Myocardial Trpc6-mediated Zn2+ Influx Induces Beneficial Positive Inotropy Through Beta-adrenoceptors)

2022 DEC 06 (NewsRx) -- By a News Reporter-Staff News Editor at Japan Daily Report -- New research on Science is the subject of a

Article Description

Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important for cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for α-adrenoceptor (αAR)-stimulated cation entry and their upregulation is associated with pathological cardiac remodeling. Whether TRPC channels participate in physiological pump functions remains unclear. We demonstrate that TRPC6-specific Zn influx potentiates β-adrenoceptor (βAR)-stimulated positive inotropy in rodent cardiomyocytes. Deletion of trpc6 impairs sympathetic nerve–activated positive inotropy but not chronotropy in mice. TRPC6-mediated Zn influx boosts αAR-stimulated βAR/G-dependent signaling in rat cardiomyocytes by inhibiting β-arrestin-mediated βAR internalization. Replacing two TRPC6-specific amino acids in the pore region with TRPC3 residues diminishes the αAR-stimulated Zn influx and positive inotropic response. Pharmacological enhancement of TRPC6-mediated Zn influx prevents chronic heart failure progression in mice. Our data demonstrate that TRPC6-mediated Zn influx with αAR stimulation enhances baroreflex-induced positive inotropy, which may be a new therapeutic strategy for chronic heart failure.

Bibliographic Details

Oda, Sayaka; Nishiyama, Kazuhiro; Furumoto, Yuka; Yamaguchi, Yohei; Nishimura, Akiyuki; Tang, Xiaokang; Kato, Yuri; Numaga-Tomita, Takuro; Kaneko, Toshiyuki; Mangmool, Supachoke; Kuroda, Takuya; Okubo, Reishin; Sanbo, Makoto; Hirabayashi, Masumi; Sato, Yoji; Nakagawa, Yasuaki; Kuwahara, Koichiro; Nagata, Ryu; Iribe, Gentaro; Mori, Yasuo; Nishida, Motohiro

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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