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 approximately 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 Ca(2+)-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 Ca(2+)-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.
Sahly
I
I
Department of Physiology, Hebrew University of Jerusalem, Israel.
Bar Nachum
S
S
Suss-Toby
E
E
Rom
A
A
Peretz
A
A
Kleiman
J
J
Byk
T
T
Selinger
Z
Z
Minke
B
B
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology*; D004331:Drosophila melanogaster / Q000235:genetics; D005136:Eye Proteins / Q000378:metabolism; D008027:Light; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010786:Photoreceptor Cells / Q000502:physiology; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D005136:Eye Proteins; D010750:Phosphoproteins; D014700:Verapamil; D004110:Diltiazem; D002118:Calcium