Enhanced transient receptor potential channel-mediated Ca2+ influx in the cells with phospholipase C-δ1 overexpression: its possible role in coronary artery spasm.

Autor: Murakami, Kazuo, Osanai, Tomohiro, Tanaka, Makoto, Nishizaki, Kimitaka, Kinjo, Takahiko, Tanno, Tomohiro, Ishida, Yuji, Suzuki, Akiko, Endo, Tomohide, Tomita, Hirofumi, Okumura, Ken
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Zdroj: Fundamental & Clinical Pharmacology; Aug2017, Vol. 31 Issue 4, p383-391, 9p
Abstrakt: We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C ( PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca2+ influx and its underlying mechanisms. We used human embryonic kidney ( HEK)-293 and coronary arteries smooth muscle cells ( CASMC). Intracellular free Ca2+ concentration ([Ca2+]i; n m) was measured by fura-2, and Ca2+ influx was evaluated by the increase in [Ca2+]i after addition of extracellular Ca2+. Acetylcholine ( ACh) was used to induce Ca2+ influx. ACh-induced peak Ca2+ influx was 19 ± 3 in control HEK-293 cells and 71 ± 8 in the cells with PLC-δ1 overexpression ( P < 0.05 between two groups). Nifedipine partially suppressed this Ca2+ influx, whereas either 2- APB or knockdown of classical transient receptor potential channel 6 ( TRPC6) blocked this Ca2+ influx. In the human CASMC, ACh-induced peak Ca2+ influx was 29 ± 6 in the control and was increased to 45 ± 16 by PLC-δ1 overexpression ( P < 0.05). Like HEK-293 cells, pretreatment with nifedipine partially suppressed Ca2+ influx, whereas either 2- APB or knockdown of TRPC6 blocked it. ACh-induced Ca2+ influx was enhanced by PLC-δ1 overexpression, and was blocked partially by nifedipine and completely by 2- APB. TRPC-mediated Ca2+ influx may be related to the enhanced Ca2+ influx in PLC-δ1 overexpression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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