Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila

Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was ≈50 times more effective than the (-)-cis isomer in blocking the Ca²⁺ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca²⁺ channels, rather than by blocking the light-sensitive channels. Application of the Ca²⁺-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [³²P]phosphate showed much greater incorporation into eye proteins of [³²P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca²⁺-channel blockers, thus, suggests that toxic increase in intracellular Ca²⁺ by means of voltage-gated Ca²⁺ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant.