Activation of calcium-sensing receptor increases TRPC3 expression in rat cardiomyocytes

Journal Article · Fri Mar 11 04:00:00 EST 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.02.033· OSTI ID:22204828

Feng, Shan-Li ^[1]; Sun, Ming-Rui ^[2]; Li, Ting-Ting; Yin, Xin ^[1]; Xu, Chang-Qing ^[3]; Sun, Yi-Hua ^[1]

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1. Department of Clinical Laboratory, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086 (China)
2. Department of Pharmacology, Qiqihaer Medical College, Qiqihaer 160001 (China)
3. Department of Pathophysiology, Harbin Medical University, Harbin 150086 (China)

Research highlights: {yields} Calcium-sensing receptor (CaR) activation stimulates TRP channels. {yields} CaR promoted transient receptor potential C3 (TRPC3) expression. {yields} Adult rat ventricular myocytes display capacitative calcium entry (CCE), which was operated by TRPCs. {yields} TRPC channels activation induced by CaR activator sustained the increased [Ca{sup 2+}]{sub i} to evoke cardiomyocytes apoptosis. -- Abstract: Transient receptor potential (TRP) channels are expressed in cardiomyocytes, which gate a type of influx of extracellular calcium, the capacitative calcium entry. TRP channels play a role in mediating Ca{sup 2+} overload in the heart. Calcium-sensing receptors (CaR) are also expressed in rat cardiac tissue and promote the apoptosis of cardiomyocytes by Ca{sup 2+} overload. However, data about the link between CaR and TRP channels in rat heart are few. In this study, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of the TRP canonical proteins TRPC1 and TRPC3 in adult and neonatal rat cardiomyocytes. Laser scan confocal microscopy was used to detect intracellular [Ca{sup 2+}]{sub i} levels in isolated adult rat ventricular myocytes. The results showed that, in adult rat cardiomyocytes, the depletion of Ca{sup 2+} stores in the endoplasmic/sarcoplasmic reticulum (ER/SR) by thapsigargin induced a transient increase in [Ca{sup 2+}]{sub i} in the absence of [Ca{sup 2+}]{sub o} and the subsequent restoration of [Ca{sup 2+}]{sub o} sustained the increased [Ca{sup 2+}]{sub i} for a few minutes, whereas, the persisting elevation of [Ca{sup 2+}]{sub i} was reduced in the presence of the TRPC inhibitor SKF96365. The stimulation of CaR by its activator gadolinium chloride (GdCl{sub 3}) or spermine also resulted in the same effect and the duration of [Ca{sup 2+}]{sub i} increase was also shortened in the absence of [Ca{sup 2+}]{sub o}. In adult and neonatal rat cardiomyocytes, GdCl{sub 3} increased the expression of TRPC3 mRNA and protein, which were reversed by SKF96365 but not by inhibitors of the L-type channels and the Na{sup +}/Ca{sup 2+} exchangers. However, GdCl{sub 3} had no obvious effect on the expression of TRPC1 protein. These results suggested that CaR stimulation induced activation of TRP channels and promoted the expression of TRPC3, but not TRPC1, that sustained the increased [Ca{sup 2+}]{sub i}.

• OSTI ID: 22204828
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 406; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CALCIUM IONS
GADOLINIUM CHLORIDES
HEART
MESSENGER-RNA
MICROSCOPY
POLYMERASE CHAIN REACTION
RATS
RECEPTORS
SARCOPLASMIC RETICULUM
SODIUM IONS
SPERMINE