Multiple H+sensors mediate the extracellular acidification-induced [Ca2+]ielevation in cultured rat ventricular cardiomyocytes.
Acidosis has been known to cause "Ca2+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 ([Ca2+]i) elevation. By using calcium imaging measures, we observed that both ASIC and TRPV1 channels inhibitors suppressed the [Ca2+]ielevation 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) Ca2+with thapsigargin or IP3receptor blocker 2-APB or PLC inhibitor U73122 significantly attenuated the elevation of [Ca2+]i, indicating that the intracellular Ca2+stores and the PLC-IP3signaling also contributed to the acidosis-induced elevation of [Ca2+]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 [Ca2+]i. These results suggest that multiple H+-sensitive receptors are involved in "Ca2+transients" induced by acidosis in the heart.
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Yuan-Lang
YL
Hu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Xue
X
Mi
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Chao
C
Huang
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Hui-Fang
HF
Wang
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Jian-Ren
JR
Song
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Qing
Q
Shu
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Lan
L
Ni
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
Jian-Guo
JG
Chen
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
Fang
F
Wang
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.|The Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan, Hubei 430030, China.|The Key Laboratory for Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
Zhuang-Li
ZL
Hu
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D015870:Gene Expression; D006352:Heart Ventricles / Q000166:cytology*; D006863:Hydrogen-Ion Concentration; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C / Q000378:metabolism; D011522:Protons; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism
C000590690:LOC102553138 protein, rat; D011522:Protons; D043562:Receptors, G-Protein-Coupled; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D015544:Inositol 1,4,5-Trisphosphate; D054801:Phosphoinositide Phospholipase C; D002118:Calcium