title: Blockade of N-type Ca2+ current by cilnidipine (FRC-8653) in acutely dissociated rat sympathetic neurones.
abstract: 1 The inhibitory effects of cilnidipine (FRC-8653) and various organic Ca2+ channel blockers on high voltage-activated Ba2+ currents (HVA IBa) in rat sympathetic neurones were examined by means of the conventional whole-cell patch-clamp recording mode under voltage-clamped conditions. 2 HVA IBa was classified into three different current components with subtype selective peptide Ca2+ channel blockers. No omega-Agatoxin IVA-sensitive (P-type) or omega-conotoxin MVIIC-sensitive (Q-type) current components were observed. Most (> 85%) IBa was found to consist of omega-conotoxin GVIA-sensitive N-type components. 3 The application of cilnidipine inhibited HVA 1Ba in a concentration-dependent manner. The Kd value for cilnidipine was 0.8 microM. Cilnidipine did not shift the current-voltage (I-V) relationship for HVA IBa, as regards the threshold potential and peak potential where the amplitude reached a maximum. 4 High concentration of three hypotensive Ca2+ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA IBa in a concentration-dependent manner. The Kd values for nifedipine, diltiazem and verapamil were 131, 151 and 47 microM, respectively. A piperazine-type Ca2+ channel blocker, flunarizine, showed a relatively potent blocking action on IBa. The Kd value was about 3 microM. 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca2+ channels which predominantly consist of an omega-Cg-GVIA-sensitive component. This blockade of the N-type Ca2+ channel, as well as the L-type Ca2+ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.
authors.affiliation: Life Science Laboratories, Ajinomoto Co., Inc., Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Uneyama
authors.forename: A
authors.initials: A
authors.lastname: Takahara
authors.forename: H
authors.initials: H
authors.lastname: Dohmoto
authors.forename: R
authors.initials: R
authors.lastname: Yoshimoto
authors.forename: K
authors.initials: K
authors.lastname: Inoue
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000818:Animals; D001464:Barium / Q000502:physiology; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D004095:Dihydropyridines; D001464:Barium; C065927:cilnidipine