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Sensitivity of Ca2+-sensing receptor-transient receptor potential-mediated Ca2+ influx to extracellular acidity in bEND.3 endothelial cells
Iat-Lon Leong1, Chung-Ming Yu2, Lian-Ru Shiao3, Paul Chan4, King-Chuen Wu5, Yuk-Man Leung3
1 Division of Cardiology, Department of Internal Medicine, Kiang Wu Hospital, Macau, China
2 Department of Anesthesiology, Chang Gung Memorial Hospital, Chiayi, Taiwan
3 Department of Physiology, China Medical University, Taichung, Taiwan
4 Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan
5 Department of Anesthesiology, Chang Gung Memorial Hospital, Chiayi; Department of Nursing, Chang Gung University of Science and Technology, Chiayi; Department of Information Management, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan
Correspondence Address:
Prof. Yuk-Man Leung
Department of Physiology, China Medical University, Taichung
Taiwan
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/0304-4920.365460
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Ca2+-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca2+. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca2+-elicited cytosolic [Ca2+] elevation) was unaffected by suppression of phospholipase C but in part involved Ca2+ influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca2+ influx triggered by high (3 mM) Ca2+ (CaSR agonist), 3 mM spermine (CaSR agonist), and 10 mM cinacalcet (positive allosteric modulator of CaSR). Extracellular acidosis (pH 6.8 and pH 6.0) strongly suppressed cytosolic [Ca2+] elevation triggered by high Ca2+, spermine, and cinacalcet; acidosis also inhibited Mn2+ influx stimulated by high Ca2+ and cinacalcet. Purinoceptor-triggered Ca2+ response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca2+ influx in acidity did not result from the reduced electrical driving force for Ca2+. Our results suggest Ca2+ influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.
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