THE CALCIUM-CHANNEL ANTAGONIST, PIMOZIDE, BLOCKS THE CYCLIC GMP-ACTIVATED CURRENT IN ROD PHOTORECEPTORS

The pharmacology of the cyclic GMP-activated current in rod photorecep tors is poorly understood, partly for a lack of suitable compounds wit h which to probe the conductance mechanism. The results described in t his study characterize the capacity of the calcium channel antagonist, pimozide, to block this cyclic GMP-activated current in excised patch es of rod plasma membrane. Pimozide blocks the cyclic GMP-activated cu rrent with half-maximal suppression at a concentration of about 0.8 mu M and nearly complete suppression at 10 muM. The block produced by pim ozide does not appear to depend on the applied voltage or on the durat ion of the voltage step. The extent of suppression was very similar fo r all voltage steps for a given concentration of pimozide. After appro priate scaling, the kinetic profiles of the cyclic GMP-activated curre nts were identical in the absence or presence of pimozide. These resul ts, then, indicate that the block by pimozide is neither relieved nor enhanced by changes in the membrane potential. The other known blocker s of the cyclic GMP-activated current, L-cis-diltiazem and dichloroben zamil, are calcium channel antagonists as well, suggesting that the cy clic GMP-activated channel may have pharmacological properties that, i n some ways, are similar to the voltage-dependent calcium channel.