Interaction of Ro 40-5967 and verapamil with the stably expressed alpha 1 subunit of the cardiac L-type calcium channel. J Pharmacol Exp Ther 274:54–63

The interaction of the nondihydropyridine calcium channel an-tagonist Ro 40-5967 with the stably expressed class C a1-subunit of the cardiac L-type calcium channel was investigated and compared with that of verapamil by using the whole cell patch clamp configuration. Both compounds blocked the Ba inward current. The IC50 values at a holding potential of-80 or-40 mV were 4.9 and 1.4 p.M for Ro 40-5967 and 250 and 15.5 p.M for verapamil. Both Ro 40-5967 and verapamil induced a partial tonic block at a holding potential of-80 mV. The block increased with high depolarization rates. Both Ro 40-5967 and verapamil shifted the steady-state inactivation curve by more than 20 mV to hyperpolarized membrane potentials and de-creased the inactivation rate constant. The effect of Ro 40-5967, but not that of verapamil, was attenuated by intracellular dialysis with GTPyS. The affinity for verapamil was not affecte