Light transduction in invertebrate hyperpolarizing photoreceptors: possible involvement of a Go-regulated guanylate cyclase.
The hyperpolarizing receptor potential of scallop ciliary photoreceptors is attributable to light-induced opening of K(+)-selective channels. Having previously demonstrated the activation of this K(+) current by cGMP, we examined upstream events in the transduction cascade. GTP-gamma-S produced persistent excitation after a flash, accompanied by decreased sensitivity and acceleration of the photocurrent, whereas GDP-beta-S only inhibited responsiveness, consistent with the involvement of a G-protein. Because G(o) (but not G(t) nor G(q)) recently has been detected in the ciliary retinal layer of a related species, we tested the effects of activators of G(o); mastoparan peptides induced an outward current suppressible by blockers of the light-sensitive conductance such as l-cis-diltiazem. In addition, intracellular dialysis with the A-protomer of pertussis toxin (PTX) depressed the photocurrent. The mechanisms that couple G-protein stimulation to changes in cGMP were investigated. Intracellular IBMX enhanced the photoresponse with little effect on the baseline current, a result that argues against regulation by light of phosphodiesterase activity. LY83583, an inhibitor of guanylate cyclase (GC), exerted a reversible, dose-dependent suppression of the photocurrent. By contrast, ODQ, an antagonist of NO-sensitive GC, and YC-1, an activator of NO-sensitive GC, failed to alter the light response or the holding current; furthermore, the NO synthase inhibitor N-methyl- l-arginine was inert, indicating that the NO signaling pathway is not implicated. Taken together, these results suggest a novel type of phototransduction cascade in which stimulation of a PTX-sensitive G(o) may activate a membrane GC to induce an increase in cGMP and the consequent opening of light-dependent channels.
Gomez
M P
MP
Department of Physiology, Boston University School of Medicine, Boston, Massachusetts 02118, and Marine Biological Laboratory, Woods Hole, Massachusetts 02543, USA.
Nasi
E
E
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008974:Mollusca; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018408:Patch-Clamp Techniques; D010455:Peptides; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010775:Photic Stimulation; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D012160:Retina / Q000166:cytology; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D014862:Wasp Venoms / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010726:Phosphodiesterase Inhibitors; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D014862:Wasp Venoms; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); C037500:mastoparan; D019001:Nitric Oxide Synthase; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D006162:Guanylate Cyclase