THE DIHYDROPYRIDINE NIGULDIPINE INHIBITS T-TYPE CA2+ CURRENTS IN ATRIAL MYOCYTES

The whole-cell tight seal recording technique was used to investigate the effects of niguldipine, a novel dihydropyridine, on Ca2+ currents in guinea pig atrial cells. Ca2+ currents were separated into T-type and L-type components by an appropriate voltage protocol. Extracellular application of 1-mu-M (+/-)-niguldipine (NIG) resulted in a pronounced blockade of both T-type (to 20 +/- 10 % of control, n = 5) and L-type Ca2+ currents (to 28 +/- 12 % of control, n = 5). Current to voltage relationships clearly showed that both Ca2+ currents were blocked over the whole voltage range examined (-60 to +40 mV). The inhibitory effect of niguldipine on T-type Ca2+ currents was found to be voltage-dependent, i. e. prolonged hyperpolarization to -90 mV led to a partial and transient removal of NIG block. The IC50 for T-type Ca2+ current inhibition by (+/-)-NIG was determined as 0.18-mu-M. NIG action is stereospecific. (+)-niguldipine was found to be more potent than (-)-niguldipine in blocking both Ca2+ currents. This study demonstrates the Ca2+ antagonistic action of the dihydropyridine NIG, which may not discriminate between T-and L-type Ca2+ channels.