Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin.
Photobleaching of rhodopsin in rod photoreceptors activates the visual cascade system leading to a decrease in cyclic GMP and the closure of cGMP-gated channels in the rod outer segment plasma membrane. Calcium plays an important role in the recovery of the rod outer segment to its dark state by regulating the resynthesis of cGMP by guanylate cyclase. Here we report that calmodulin, a Ca(2+)-binding protein present in the rod outer segment, increases the apparent Michaelis constant of the channel for cGMP. This results in a decrease in the rate of cation influx into the rod outer segment by two- to sixfold at low cGMP concentrations and has the effect of increasing the sensitivity of the channel to small changes in cGMP levels during phototransduction. Biochemical studies indicate that calcium-calmodulin binds to a protein of M(r) 240K which is tightly associated with the channel. On the basis of these studies, Ca2+ is suggested to play a central role in photorecovery and light adaptation, not only by regulating guanylate cyclase, possibly through recoverin, but also by modulating the cGMP-gated channel through calmodulin interaction with the 240K protein.
Hsu
Y T
YT
Department of Biochemistry, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Molday
R S
RS
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology*; D002417:Cattle; D015815:Cell Adhesion Molecules; D054407:Chemokine CCL4; D054815:Cyclic Nucleotide-Gated Cation Channels; D016207:Cytokines; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology*; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011509:Proteoglycans; D012374:Rod Cell Outer Segment / Q000187:drug effects* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1
D002147:Calmodulin; D015815:Cell Adhesion Molecules; D054407:Chemokine CCL4; D054815:Cyclic Nucleotide-Gated Cation Channels; D016207:Cytokines; D007473:Ion Channels; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011509:Proteoglycans; D019010:Vascular Cell Adhesion Molecule-1; D002118:Calcium