BLOCKADE OF N-TYPE CA2-8653) IS ACUTELY DISSOCIATED RAT SYMPATHETIC NEURONS( CURRENT BY CILNIDIPINE (FRC)

1 The inhibitory effects of cilnidipine (FRC-8653) and Various organic Ca2+ channel blockers on high voltage-activated Ba2+ currents (HVA I- Ba) in rat sympathetic neurones were examined by means of the conventi onal whole-cell patch-clamp recording mode under voltage-clamped condi tions. 2 HVA I-ba was classified into three different current componen ts with subtype selective peptide Ca2+ channel blockers. No omega-Agat oxin IVA-sensitive (P-type) or omega-conotoxin MVIIC-sensitive (Q-type ) current components were observed. Most (>85%) I-Ba was found to cons ist of omega-conotoxin GVIA-sensitive N-type components. 3 The applica tion of cilnidipine inhibited HVA I-Ba in a concentration-dependent ma nner. The K-d value for cilnidipine was 0.8 mu 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 Ca2+ channel bl ockers, nifedipine, diltiazem and verapamil, all inhibited HVA I-Ba in a concentration-dependent manner. The K-d Values for nifedipine, dilt iazem and verapamil were 131, 151 and 47 mu M, respectively. A piperaz ine-type Ca2+ channel blocker, flunarizine, showed a relatively potent blocking action on I-Ba The K-d value was about 3 mu M. 5 These resul ts thus show that cilnidipine potently inhibits the sympathetic Ca2+ c hannels which predominantly consist of an omega-Cg-GVIA-sensitive comp onent. This blockade of the N-type Ca2+ channel, as well as the L-type Ca2+ channel by cilnidipine suggests that it could be used therapeuti cally for treatment of hypersensitive sympathetic disorders associated with hypertension.