Effect of nilvadipine on the voltage-dependent Ca2+ channels in rat hippocampal CA1 pyramidal neurons

Effects of nilvadipine on the low- and high-voltage activated Ca2+ currents (LVA and HVA I-Ca, respectively) were compared with other organic Ca2+ antagonists in acutely dissociated rat hippocampal CAI 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(50)s) at every 1- and 30-s stimulation were 6.3 X 10(-7) M and 1.8 X 10(-6) M for flunarizine, 1.9 X 10(-6) M and 7.6 x 10(-6) M for nilvadipine, and 4.0 X 10(-6) M and 8.0 X 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 IC50 of 1.5 X 10(-7) M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 34% of the total HVA I-Ca. On the other hand, amlodipine non-selectively inhibited the HVA Ca2+ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx through both LVA and HVA. L-type Ca2+ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia. (C) 1998 Published by Elsevier Science B.V. All rights reserved.