Blockade of N‐type Ca2+ current by cilnidipine (FRC‐8653) in acutely dissociated rat sympathetic neurones

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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 ω‐Agatoxin IVA‐sensitive (P‐type) or ω‐conotoxin MVIIC‐sensitive (Q‐type) current components were observed. Most (>85%) IBa was found to consist of ω‐conotoxin GVIA‐sensitive N‐type components. 3 The application of cilnidipine inhibited HVA IBa in a concentration‐dependent manner. The Kd value for cilnidipine was 0.8 μM. 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 concentrations 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 μM, respectively. A piperazine‐type Ca2+ channel blocker, flunarizine, showed a relatively potent blocking action on IBa. The Kd value was about 3 μM. 5 These results thus show that cilnidipine potently inhibits the sympathetic Ca2+ channels which predominantly consist of an ω‐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. British Journal of Pharmacology (1997) 122, 37–42; doi:10.1038/sj.bjp.0701342

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