Calcium-sensing receptor activation contributed to apoptosis stimulates TRPC6 channel in rat neonatal ventricular myocytes |
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Authors: | Yi-hua Sun Yong-quan Li Shan-li Feng Zhen-wei Pan Ting-ting Li |
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Institution: | a Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China b Harbin Medical University, Harbin 150086, China c Department of Pharmacology, Harbin Medical University, Harbin 150086, China d Department of Pathophysiology, Harbin Medical University, Harbin 150086, China |
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Abstract: | Capacitative calcium entry (CCE) refers to the influx of calcium through plasma membrane channels activated on depletion of endoplasmic sarcoplasmic/reticulum (ER/SR) Ca2+ stores, which is performed mainly by the transient receptor potential (TRP) channels. TRP channels are expressed in cardiomyocytes. Calcium-sensing receptor (CaR) is also expressed in rat cardiac tissue and plays an important role in mediating cardiomyocyte apoptosis. However, there are no data regarding the link between CaR and TRP channels in rat heart. In this study, in rat neonatal myocytes, by Ca2+ imaging, we found that the depletion of ER/SR Ca2+ stores by thapsigargin (TG) elicited a transient rise in cytoplasmic Ca2+ (Ca2+]i), followed by sustained increase depending on extracellular Ca2+. But, TRP channels inhibitor (SKF96365), not L-type channels or the Na+/Ca2+ exchanger inhibitors, inhibited Ca2+]i relatively high. Then, we found that the stimulation of CaR with its activator gadolinium chloride (GdCl3) or by an increased extracellular Ca2+(Ca2+]o) increased the concentration of intracelluar Ca2+, whereas, the sustained elevation of Ca2+]i was reduced in the presence of SKF96365. Similarly, the duration of Ca2+]i increase was also shortened in the absence of extracellular Ca2+. Western blot analysis showed that GdCl3 increased the expression of TRPC6, which was reversed by SKF96365. Additionally, SKF96365 reduced cardiomyocyte apoptosis induced by GdCl3. Our results suggested that CCE exhibited in rat neonatal myocytes and CaR activation induced Ca2+-permeable cationic channels TRPCs to gate the CCE, for which TRPC6 was one of the most likely candidates. TRPC6 channel was functionally coupled with CaR to enhance the cardiomyocyte apoptosis. |
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Keywords: | Calcium-sensing receptor Transient receptor potential channels Apoptosis Cardiomyocyte |
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