摘要：Acidosis has been known to cause "Ca(2+) transients", however, the mechanism is still uncertain. Here, we demonstrated that multiple H(+) sensors, such as ASICs, TRPV1 and proton-sensing G protein coupled receptors (GPCRs) are involved in extracellular acidification-induced intracellular calcium ([Ca(2+)]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca(2+)]i elevation induced by extracellular acidosis in cultured rat cardiac myocytes. Then, both channels mRNA and proteins were identified by RT-PCR, western blotting and immunofluorescence. ASIC-like and TRPV1-like currents were induced by extracellular acidification, suggesting that functional ASIC and TRPV1 channels jointly mediated extracellular calcium entry. Furthermore, either pre-exhaustion of sarcoplasmic reticulum (SR) Ca(2+) with thapsigargin or IP3 receptor blocker 2-APB or PLC inhibitor U73122 significantly attenuated the elevation of [Ca(2+)]i, indicating that the intracellular Ca(2+) stores and the PLC-IP3 signaling also contributed to the acidosis-induced elevation of [Ca(2+)]i. By using genetic and pharmacological approaches, we identified that ovarian cancer G protein-coupled receptor 1 (OGR1) might be another main component in acidosis-induced release of [Ca(2+)]i. These results suggest that multiple H(+)-sensitive receptors are involved in "Ca(2+) transients" induced by acidosis in the heart.
