The excitation cascade of Limulus ventral photoreceptors: guanylate cyclase as the link between InsP3-mediated Ca2+ release and the opening of cGMP-gated channels.
BACKGROUND
Early stages in the excitation cascade of Limulus photoreceptors are mediated by activation of Gq by rhodopsin, generation of inositol-1,4,5-trisphosphate by phospholipase-C and the release of Ca2+. At the end of the cascade, cGMP-gated channels open and generate the depolarizing receptor potential. A major unresolved issue is the intermediate process by which Ca2+ elevation leads to channel opening.


RESULTS
To explore the role of guanylate cyclase (GC) as a potential intermediate, we used the GC inhibitor guanosine 5'-tetraphosphate (GtetP). Its specificity in vivo was supported by its ability to reduce the depolarization produced by the phosphodiesterase inhibitor IBMX. To determine if GC acts subsequent to InsP3 production in the cascade, we examined the effect of intracellular injection of GtetP on the excitation caused by InsP3 injection. This form of excitation and the response to light were both greatly reduced by GtetP, and they recovered in parallel. Similarly, GtetP reduced the excitation caused by intracellular injection of Ca2+. In contrast, this GC inhibitor did not affect the excitation produced by injection of a cGMP analog.


CONCLUSIONS
We conclude that GC is downstream of InsP3-induced Ca2+ release and is the final enzymatic step of the excitation cascade. This is the first invertebrate rhabdomeric photoreceptor for which transduction can be traced from rhodopsin photoisomerization to ion channel opening.
Garger
Alexander V
AV
Department of Biology and Center for Complex Systems, Brandeis University, Waltham, MA 02454-9110, USA. alexander_garger@nymc.edu
Richard
Edwin A
EA
Lisman
John E
JE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006737:Horseshoe Crabs / Q000502:physiology*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism* / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects / Q000378:metabolism; D010775:Photic Stimulation; D017956:Photoreceptor Cells, Invertebrate / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D004791:Enzyme Inhibitors; D010726:Phosphodiesterase Inhibitors; D013873:Thionucleotides; D015544:Inositol 1,4,5-Trisphosphate; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium