Open AccessMultiple H+ sensors mediate the extracellular acidification-induced [Ca2+]i elevation in cultured rat ventricular cardiomyocytes
Author(s) -
Yuan-Lang Hu,
Xue Mi,
Chao Huang,
HuiFang Wang,
Jianren Song,
Qing Shu,
Lan Ni,
Jianguo Chen,
Fang Wang,
ZhuangLi Hu
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep44951
Subject(s) - extracellular , thapsigargin , calcium , intracellular , calcium in biology , trpv1 , acidosis , receptor , myocyte , calcium signaling , t type calcium channel , endoplasmic reticulum , voltage dependent calcium channel , inositol trisphosphate receptor , chemistry , biology , microbiology and biotechnology , medicine , endocrinology , transient receptor potential channel , biochemistry , inositol
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 IP 3 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-IP 3 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.