Effect of nilvadipine on high-voltage activated Ca2+ channels in rat CNS neurons.
The effect of nilvadipine, a dihydropyridine derivative, on high-voltage activated (HVA) Ca2+ channels was investigated in freshly dissociated rat frontal cortical neurons. The cortical neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of the L-, N-, P-, O- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 23% of the total HVA Ca2+ channel current. A reversible inhibitory effect of nilvadipine on the L-type Ca2+ channel current was also observed in a concentration-dependent fashion without affecting the current-voltage relationship. The half-maximum inhibitory concentration was 3 x 10(-8) M. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx, in combination with the cerebral vasodilatory action, may prevent neuronal damage during brain ischemia.
Ishibashi
H
H
Department of Physiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Rhee
J S
JS
Akaike
N
N
D000818:Animals; D001921:Brain / Q000502:physiology*; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020746:Calcium Channels, L-Type; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D002104:Cadmium; C035100:nilvadipine; C075851:omega-conotoxin-MVIIC; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; D009543:Nifedipine