The effect of a new type of organic Ca2+ channel blocker, NC-1100 [(±)-1-(3,4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl)ethanol dihydrochloride], on both low- and high-threshold Ca2+ currents was studied in the whole-cell mode of the pyramidal neurons freshly dissociated from rat hippocampal CA1 region under voltage-clamp condition. The NC-1100 reversibly reduced the high-threshold Ca2+ current (HVA ICa) in a concentration-dependent manner without affecting the current-voltage relationship. The values of half-inhibition (IC50) were 1.3 × 10-5 and 9.1 × 10-6 M in external solution containing 10 and 2.5 mM Ca2+, respectively. The NC-1100 also decreased the low-threshold Ca2+ current (LVA ICa) in a concentration-dependent manner. The inhibitory potency was augmented by increasing the stimulation frequency and / or decreasing the extracellular Ca2+ concentration to a physiological range (2.5 mM). The IC50 value decreased to 7.7 × 10-7 M in external solution containing 2.5 mM Ca2+ at a stimulation frequency of 1 Hz. The NC-1100 delayed the reactivation of LVA Ca2+ channel and enhanced voltage-dependently the steady-state inactivation, suggesting that this drug bound not only the resting LVA Ca2+ channel but also the inactivated one.
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