The calcium channel antagonist, pimozide, blocks the cyclic GMP-activated current in rod photoreceptors.

The pharmacology of the cyclic GMP-activated current in rod photoreceptors is poorly understood, partly for a lack of suitable compounds with which to probe the conductance mechanism. The results described in this study characterize the capacity of the calcium channel antagonist, pimozide, to block this cyclic GMP-activated current in excised patches of rod plasma membrane. Pimozide blocks the cyclic GMP-activated current with half-maximal suppression at a concentration of about 0.8 microM and nearly complete suppression at 10 microM. The block produced by pimozide does not appear to depend on the applied voltage or on the duration of the voltage step. The extent of suppression was very similar for all voltage steps for a given concentration of pimozide. After appropriate scaling, the kinetic profiles of the cyclic GMP-activated currents were identical in the absence or presence of pimozide. These results, then, indicate that the block by pimozide is neither relieved nor enhanced by changes in the membrane potential. The other known blockers of the cyclic GMP-activated current, L-cis-diltiazem and dichlorobenzamil, are calcium channel antagonists as well, suggesting that the cyclic GMP-activated channel may have pharmacological properties that, in some ways, are similar to the voltage-dependent calcium channel.