title: Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors.
abstract: The retina's photoreceptor cells adjust their sensitivity to allow photons to be transduced over a wide range of light intensities. One mechanism thought to participate in sensitivity adjustments is Ca(2+) regulation of guanylate cyclase (GC) by guanylate cyclase-activating proteins (GCAPs). We evaluated the contribution of GCAPs to sensitivity regulation in rods by disrupting their expression in transgenic mice. The GC activity from GCAPs-/- retinas showed no Ca(2+) dependence, indicating that Ca(2+) regulation of GCs had indeed been abolished. Flash responses from dark-adapted GCAPs-/- rods were larger and slower than responses from wild-type rods. In addition, the incremental flash sensitivity of GCAPs-/- rods failed to be maintained at wild-type levels in bright steady light. GCAP2 expressed in GCAPs-/- rods restored maximal light-induced GC activity but did not restore normal flash response kinetics. We conclude that GCAPs strongly regulate GC activity in mouse rods, decreasing the flash sensitivity in darkness and increasing the incremental flash sensitivity in bright steady light, thereby extending the rod's operating range.
authors.affiliation: The Mary D. Allen Laboratory for Vision Research, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles 90089-9112, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mendez
authors.forename: M E
authors.initials: ME
authors.lastname: Burns
authors.forename: I
authors.initials: I
authors.lastname: Sokal
authors.forename: A M
authors.initials: AM
authors.lastname: Dizhoor
authors.forename: W
authors.initials: W
authors.lastname: Baehr
authors.forename: K
authors.initials: K
authors.lastname: Palczewski
authors.forename: D A
authors.initials: DA
authors.lastname: Baylor
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D006152:Cyclic GMP / Q000502:physiology*; D003624:Darkness; D004789:Enzyme Activation; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000378:metabolism*; D051604:Guanylate Cyclase-Activating Proteins; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010775:Photic Stimulation; D010777:Photochemistry; D011993:Recombinant Fusion Proteins / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology / Q000528:radiation effects*; D015290:Second Messenger Systems / Q000502:physiology*; D012684:Sensory Thresholds / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D005136:Eye Proteins; D051604:Guanylate Cyclase-Activating Proteins; C496737:Guca1a protein, mouse; C496740:Guca1b protein, mouse; D011993:Recombinant Fusion Proteins; D006162:Guanylate Cyclase; D006152:Cyclic GMP