Effect of nilvadipine on the voltage-dependent Ca 2+ channels in rat hippocampal CA1 pyramidal neurons

Abstract

Effects of nilvadipine on the low- and high-voltage activated Ca 2+ currents (LVA and HVA I Ca, respectively) were compared with other organic Ca 2+ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA I Ca were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC 50s) at every 1- and 30-s stimulation were 6.3×10 −7 M and 1.8×10 −6 M for flunarizine, 1.9×10 −6 M and 7.6×10 −6 M for nilvadipine, and 4.0×10 −6 M and 8.0×10 −6 M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA I Ca in a concentration-dependent manner with an IC 50 of 1.5×10 −7 M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca 2+ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca 2+ channel current which comprised 34% of the total HVA I Ca. On the other hand, amlodipine non-selectively inhibited the HVA Ca 2+ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca 2+ influx through both LVA and HVA L-type Ca 2+ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia.