Multiple H+ sensors mediate the extracellular acidification-induced [Ca2+]i elevation in cultured rat ventricular cardiomyocytes

• Published in: Scientific reports 2017-03, Vol.7 (1), p.44951-44951, Article 44951
• Main Authors: Hu, Yuan-Lang, Mi, Xue, Huang, Chao, Wang, Hui-Fang, Song, Jian-Ren, Shu, Qing, Ni, Lan, Chen, Jian-Guo, Wang, Fang, Hu, Zhuang-Li
• Format: Article
• Language: English
• Subjects: 13/51; 13/95; 631/45/269/1149; 692/4019/592/75; 82/80; Acidification; Acidity; Acidosis; Animals; Calcium; Calcium (extracellular); Calcium (intracellular); Calcium (reticular); Calcium - metabolism; Calcium channels; Calcium imaging; Calcium Signaling; Capsaicin receptors; Cardiac muscle; Cardiomyocytes; Cells, Cultured; Extracellular Space - metabolism; G protein-coupled receptors; Gene Expression; Heart diseases; Heart Ventricles - cytology; Humanities and Social Sciences; Hydrogen; Hydrogen-Ion Concentration; Immunofluorescence; Inositol 1,4,5-Trisphosphate - metabolism; Intracellular; Intracellular signalling; Models, Biological; mRNA; multidisciplinary; Myocytes; Myocytes, Cardiac - metabolism; Ovarian cancer; Phosphoinositide Phospholipase C - metabolism; Polymerase chain reaction; Protons; Rats; Receptors, G-Protein-Coupled - metabolism; Rodents; Sarcoplasmic Reticulum - metabolism; Science; Sensors; Signal Transduction; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Ventricle; Western blotting
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep44951

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.