Role of transient receptor potential protein 7(TRP7), receptor-activated Ca^<2+> channels, in myocardial apoptosis

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We performed 1)In vitro study using cultured cells and 2)In vivo study using a rat model with heart failure.1)TRP7 transfection study using HEK293 cells and rat neonatal cultured cardiomyocytes.(1)Ca^<2+>-transient activated by carbachol was augmented in TRP7-transfected HEK cells more than in non-transfected cells, suggesting that TRP7 acts as G protein-coupled Ca^<2+> channels.(2)Apoptosis was induced in TRP7-transfected myocardial cells, and the incidence of apoptosis was further increased when activated by angiotensin II(Ang II), as detected by TUNEL stain. The Ang II-induced apoptosis was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.(3)In apoptotic cells, the expression of atrial natriuretic factor(ANF) was decreased, and the destruction of actin fibers was noted.(4)The expression of TRP7 mRNA was increased by Ang II, and this increase was inhibited by Ang II receptor blocker, Ca^<2+> channel blocker, and calcineurin inhibitor.2)Role of TRP7 in Dahl salt-sensitive rats with heart, failure.(1)The expression of TRP7 mRNA was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.(2)Apoptosis was increased in the myocardium of heart failure rats, and this increase was inhibited by long-term treatment with an angiotensin-converting enzyme inhibitor.Based on these results, TRP7 may act as receptor-activated Ca^<2+> channels mediating Ang II-induced myocardial apoptosis via calcineurin-dependent pathway, and this signaling may contribute to the process of apoptosis leading to heart failure.