Effect of 11-cis 13-demethylretinal on phototransduction in bleach-adapted rod and cone photoreceptors.
We used 11-cis 13-demethylretinal to examine the physiological consequences of retinal's noncovalent interaction with opsin in intact rod and cone photoreceptors during visual pigment regeneration. 11-Cis 13-demethylretinal is an analog of 11-cis retinal in which the 13 position methyl group has been removed. Biochemical experiments have shown that it is capable of binding in the chromophore pocket of opsin, forming a Schiff-base linkage with the protein to produce a pigment, but at a much slower rate than the native 11-cis retinal (Nelson, R., J. Kim deReil, and A. Kropf. 1970. Proc. Nat. Acad. Sci. USA. 66:531-538). Experimentally, this slow rate of pigment formation should allow separate physiological examination of the effects of the initial binding of retinal in the pocket and the subsequent formation of the protonated Schiff-base linkage. Currents from solitary rods and cones from the tiger salamander were recorded in darkness before and after bleaching and then after exposure to 11-cis 13-demethylretinal. In bleach-adapted rods, 11-cis 13-demethylretinal caused transient activation of phototransduction, as evidenced by a decrease of the dark current and sensitivity, acceleration of the dim flash responses, and activation of cGMP phosphodiesterase and guanylyl cyclase. The steady state of phototransduction activity was still higher than that of the bleach-adapted rod. In contrast, exposure of bleach-adapted cones to 11-cis 13-demethylretinal resulted in an immediate deactivation of transduction as measured by the same parameters. These results extend the validity of a model for the effects of the noncovalent binding of a retinoid in the chromophore pockets of rod and cone opsins to analogs capable of forming a Schiff-base and imply that the noncovalent binding by itself may play a role for the dark adaptation of photoreceptors.
Corson
D W
DW
Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston 29425, USA.
Kefalov
V J
VJ
Cornwall
M C
MC
Crouch
R K
RK
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000221:Adaptation, Ocular / Q000187:drug effects / Q000502:physiology*; D000557:Ambystoma; D000818:Animals; D003623:Dark Adaptation / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D006162:Guanylate Cyclase / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology*; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology*; D012172:Retinaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D017299:Rod Opsins / Q000378:metabolism; D015293:Transducin / Q000378:metabolism; D014785:Vision, Ocular / Q000187:drug effects* / Q000502:physiology*
C413304:13-demethylretinal; D010726:Phosphodiesterase Inhibitors; D017299:Rod Opsins; D010727:Phosphoric Diester Hydrolases; D015293:Transducin; D006162:Guanylate Cyclase; D012172:Retinaldehyde; D015056:1-Methyl-3-isobutylxanthine