Abstract
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 μM (±)-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 μM. 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.
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Romanin, C., Seydl, K., Glossmann, H. et al. The dihydropyridine niguldipine inhibits T-type Ca2+ currents in atrial myocytes. Pflügers Arch 420, 410–412 (1992). https://doi.org/10.1007/BF00374478
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DOI: https://doi.org/10.1007/BF00374478