2020-A01-K07-Nishida

A01:Molecular basis underlying Zn2+-dependent regulation of sympathetic nerve-stimulated cardiac response
Motohiro NISHIDA
(Graduate School of Pharmaceutical Sciences, Kyushu University / Exploratory Research Center on Life and Living Systems, National Institutes of Natural Sciences)
Lab website

Autonomic nervous regulation of cardiac function plays an essential role in the maintenance of Cardiocirculatory homeostasis. This study aims to elucidate the role of local Zn2+ influx in cardiotonic action induced by sympathetic nervous stimulation. It is generally thought that noradrenaline released from sympathetic nerve endings stimulates β-adrenergic receptors expressing on cardiac cell membranes, leading to increases in cardiac contractility (inotropy) and beating rate (chronotropy). Although noradrenaline is a true endogenous but low-affinity ligand compared to isoproterenol, an artificial but high-affinity ligand, how noradrenaline is sufficient to stimulate β-adrenergic receptors and enhance cardiac contractility has been overlooked. We are approaching the true mechanism underlying positive inotropic effect by sympathetic nervous stimulation, focusing on receptor-activated Zn2+ permeable transient receptor potential (TRP) channel.

Major publications
Nishiyama K, Numaga-Tomita T, Fujimoto Y, Tanaka T, Toyama C, Nishimura A, Yamashita T, Matsunaga N, Koyanagi S, Azuma YT, Ibuki Y, Uchida K, Ohdo S, Nishida M.
“Ibudilast attenuates doxorubicin-induced cytotoxicity by suppressing formation of TRPC3-Nox2 protein complex”
Br. J. Pharmacol. 2019 Sep;176(18):3723-3738.
doi: 10.1111/bph.14777.

Shimauchi T, Numaga-Tomita T, Ito T, Nishimura A, Matsukane R, Oda S, Hoka S, Ide T, Koitabashi N, Uchida K, Sumimoto H, Mori Y, Nishida M
“TRPC3-Nox2 complex mediates doxorubicin-induced myocardial atrophy.”
JCI Insight. 2017 Aug 3;2(15). pii: 93358.
doi: 10.1172/jci.insight.93358.

Onohara N, Nishida M, Inoue R, Kobayashi H, Sumimoto H, Sato Y, Mori Y, Nagao T, Kurose H.
“TRPC3 and TRPC6 are essential for angiotensin II-induced cardiac hypertrophy.”
EMBO J. 2006 Nov 15;25(22):5305-5316.
doi: 10.1038/sj.emboj.7601417