Enhanced transient receptor potential channel-mediated Ca2+ influx in the cells with phospholipase C-δ1 overexpression: its possible role in coronary artery spasm.
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) (nM) 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 2 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.
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