Inhibition of L-type Ca2+ channel by mitochondrial Na+–Ca2+ exchange inhibitor CGP-37157 in rat atrial myocytes

7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepine-2(3H)-one (CGP-37157) inhibits mitochondrial Na+–Ca2+ exchange. It is often used as an experimental tool for studying the role of the mitochondrial Na+–Ca2+ exchanger in Ca2+ signaling. Because the selectivity of CGP-37157 in adult cardiomyocytes has not been confirmed, we tested whether CGP-37157 affects the L-type Ca2+ channel using a whole-cell patch-clamp in adult rat atrial myocytes. We found that CGP-37157 suppressed L-type Ca2+ current (ICa) with IC50 of ∼ 0.27 μM, without altering the voltage dependence of the current–voltage relationships. CGP-37157 inhibited the Ba2+ current (IBa) through the Ca2+ channel with a similar dose–response. The inhibitory effects of CGP-37157 on ICa or IBa were resistant to the intracellular Ca2+ buffering. Intracellular application of CGP-37157 did not significantly alter ICa. The combination of CGP-37157 with known Ca2+ channel inhibitor diltiazem yielded antagonism consistent with additivity of response. Our data suggest that CGP-37157 directly suppresses the L-type Ca2+ channel in intact adult cardiomyocytes.