Blockade of N‐type Ca 2+ current by cilnidipine (FRC‐8653) in acutely dissociated rat sympathetic neurones

1 The inhibitory effects of cilnidipine (FRC‐8653) and various organic Ca 2+ channel blockers on high voltage‐activated Ba 2+ currents (HVA I Ba ) in rat sympathetic neurones were examined by means of the conventional whole‐cell patch‐clamp recording mode under voltage‐clamped conditions. 2 HVA I Ba was classified into three different current components with subtype selective peptide Ca 2+ channel blockers. No ω‐Agatoxin IVA‐sensitive (P‐type) or ω‐conotoxin MVIIC‐sensitive (Q‐type) current components were observed. Most (>85%) I Ba was found to consist of ω‐conotoxin GVIA‐sensitive N‐type components. 3 The application of cilnidipine inhibited HVA I Ba in a concentration‐dependent manner. The K d value for cilnidipine was 0.8 μ M . Cilnidipine did not shift the current‐voltage ( I ‐V) relationship for HVA I Ba , as regards the threshold potential and peak potential where the amplitude reached a maximum. 4 High concentrations of three hypotensive Ca 2+ channel blockers, nifedipine, diltiazem and verapamil, all inhibited HVA I Ba in a concentration‐dependent manner. The K d values for nifedipine, diltiazem and verapamil were 131, 151 and 47 μ M , respectively. A piperazine‐type Ca 2+ channel blocker, flunarizine, showed a relatively potent blocking action on I Ba . The K d value was about 3 μ M . 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca 2+ channels which predominantly consist of an ω‐Cg‐GVIA‐sensitive component. This blockade of the N‐type Ca 2+ channel, as well as the L‐type Ca 2+ channel by cilnidipine suggests that it could be used therapeutically for treatment of hypersensitive sympathetic disorders associated with hypertension.British Journal of Pharmacology (1997) 122 , 37–42; doi: 10.1038/sj.bjp.0701342