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 ICa, respectively) were compared with other organic Ca2+ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA ICa were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC50s) at every 1- and 30-s stimulation were 6.3x10-7 M and 1.8x10-6 M for flunarizine, 1.9x10-6 M and 7.6x10-6 M for nilvadipine, and 4.0x10-6 M and 8.0x10-6 M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA ICa in a concentration-dependent manner with an IC50 of 1.5x10-7 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 ICa. 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.
Ishibashi
H
H
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
Murai
Y
Y
Akaike
N
N
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005444:Flunarizine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; C035100:nilvadipine; D017311:Amlodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009543:Nifedipine; D005444:Flunarizine