EFFECT OF SR33805 ON BARIUM CURRENT AND ASYMMETRIC INTRAMEMBRANE CHARGE MOVEMENT IN FRESHLY DISSOCIATED MOUSE CEREBELLAR PURKINJE NEURONS

SR33805 is a novel calcium channel blocker that binds selectively and with high affinity to the alpha 1 subunit of the L-type calcium channe l. The binding site for SR33805 is distinct from other classical calci um channel blockers although they interact allosterically. The block b y SR33805 of the neuronal L-type calcium current has been reported [Ro mey, G. and Lazdunski, M., J. Pharmacol. Exp. Ther., 271 (1994) 1348-1 352.]. In Purkinje neurons, the L-type calcium current is nearly absen t. Nevertheless, we have shown the presence of intramembrane charge mo vement related to the dihydropyridines (DHP) receptor in these neurons . We show here that SR33805 has no effect on barium currents recorded in Purkinje cells but is a very potent blocker of intramembrane charge movement. It reduces charge movement to 48% of control with an IC50 o f 0.5 nM.