Abstract
7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepine-2( 3H)-one (CGP-37157) inhibits mitochondrial Na +–Ca 2+ exchange. It is often used as an experimental tool for studying the role of the mitochondrial Na +–Ca 2+ exchanger in Ca 2+ signaling. Because the selectivity of CGP-37157 in adult cardiomyocytes has not been confirmed, we tested whether CGP-37157 affects the L-type Ca 2+ channel using a whole-cell patch-clamp in adult rat atrial myocytes. We found that CGP-37157 suppressed L-type Ca 2+ current ( I Ca) with IC 50 of ∼ 0.27 μM, without altering the voltage dependence of the current–voltage relationships. CGP-37157 inhibited the Ba 2+ current ( I Ba) through the Ca 2+ channel with a similar dose–response. The inhibitory effects of CGP-37157 on I Ca or I Ba were resistant to the intracellular Ca 2+ buffering. Intracellular application of CGP-37157 did not significantly alter I Ca. The combination of CGP-37157 with known Ca 2+ channel inhibitor diltiazem yielded antagonism consistent with additivity of response. Our data suggest that CGP-37157 directly suppresses the L-type Ca 2+ channel in intact adult cardiomyocytes.
Published Version
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