Abstract

We investigated the effects of cilnidipine, a dihydropyridine derivative, on neuronal Ca⁺⁺ channels in rat dorsal root ganglion neurons. Voltage-dependent Ca⁺⁺-channel currents were recorded, using 5 mM Ba⁺⁺ as the charge carrier, by means of the whole-cell patch-clamp technique. The Ba⁺⁺current was subdivided pharmacologically into calciseptine-sensitive (L-type), ω-conotoxin GVIA- (ωCgTx) sensitive (N-type), ω-agatoxin IVA- (ωAgTx) sensitive (P/Q-type) and toxin-resistant currents. Cilnidipine inhibited the L-type current with an IC₅₀ of 100 nM in neurons pretreated with ωCgTx plus ωAgTx. In neurons pretreated with Cal plus ωAgTx, cilnidipine induced a potent inhibition of the N-type current, but was unable to block the residual Ba⁺⁺ current. The IC₅₀ for cilnidipine in respect of the N-type current was 200 nM. Cilnidipine (300–500 nM) modified neither the voltage-dependent inactivation curve nor the decay of the N-type current. Furthermore, elevation of the holding potential did not enhance the inhibitory action of cilnidipine (300 nM) on the N-type current. No effect was induced by 100 nM cilnidipine on the P/Q-type current. However, nicardipine (1 μM) barely inhibited the N-type current at a concentration that almost completely blocked the L-type current. In conclusion, cilnidipine has potent inhibitory actions on N-type as well as L-type voltage-dependent Ca⁺⁺-channel in rat dorsal root ganglion neurons. The former action may bestow an additional clinical advantage for the treatment of hypertension, such as suppression of reflex tachycardia.