Leong Iat-Lon, Yu Chung-Ming, Shiao Lian-Ru, Chan Paul, Wu King-Chuen, Leung Yuk-Man
Division of Cardiology, Department of Internal Medicine, Kiang Wu Hospital, Macau, China.
Department of Anesthesiology, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Chin J Physiol. 2022 Nov-Dec;65(6):277-281. doi: 10.4103/0304-4920.365460.
Ca-sensing receptors (CaSRs) are G protein-coupled receptors activated by elevated concentrations of extracellular Ca. In our previous works, we showed protein and functional expression of CaSR in mouse cerebral endothelial cell (EC) (bEND.3); the CaSR response (high Ca-elicited cytosolic [Ca] elevation) was unaffected by suppression of phospholipase C but in part involved Ca influx through transient receptor potential V1 (TRPV1) channels. In this work, we investigated if extracellular acidity affected CaSR-mediated Ca influx triggered by high (3 mM) Ca (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 [Ca] elevation triggered by high Ca, spermine, and cinacalcet; acidosis also inhibited Mn influx stimulated by high Ca and cinacalcet. Purinoceptor-triggered Ca response, however, was not suppressed by acidosis. Extracellular acidity also did not affect membrane potential, suggesting suppressed CaSR-mediated Ca influx in acidity did not result from the reduced electrical driving force for Ca. Our results suggest Ca influx through a putative CaSR-TRP complex in bEND.3 EC was sensitive to extracellular pH.
钙敏感受体（CaSRs）是由细胞外钙浓度升高激活的G蛋白偶联受体。在我们之前的研究中，我们展示了CaSR在小鼠脑内皮细胞（EC）（bEND.3）中的蛋白表达和功能表达；CaSR反应（高钙引起的胞质[Ca]升高）不受磷脂酶C抑制的影响，但部分涉及通过瞬时受体电位V1（TRPV1）通道的钙内流。在这项研究中，我们研究了细胞外酸度是否会影响由高钙（3 mM）、3 mM精胺（CaSR激动剂）和10 mM西那卡塞（CaSR的正变构调节剂）触发的CaSR介导的钙内流。细胞外酸中毒（pH 6.8和pH 6.0）强烈抑制了由高钙、精胺和西那卡塞触发的胞质[Ca]升高；酸中毒也抑制了由高钙和西那卡塞刺激的锰内流。然而，嘌呤受体触发的钙反应不受酸中毒的抑制。细胞外酸度也不影响膜电位，这表明在酸性条件下抑制的CaSR介导的钙内流不是由钙的电驱动力降低引起的。我们的结果表明，bEND.3内皮细胞中通过假定的CaSR-TRP复合物的钙内流对细胞外pH敏感。
