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The Journal of Neuroscience, March 15, 2000, 20(6):2209-2217

Mice Lacking G-Protein Receptor Kinase 1 Have Profoundly Slowed Recovery of Cone-Driven Retinal Responses

A. L. Lyubarsky¹, C.-K. Chen², M. I. Simon², and E. N. Pugh Jr¹

¹ Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and ² Division of Biology, California Institute of Technology, Pasadena, California 91125

G-Protein receptor kinase 1 (GRK1) ("rhodopsin kinase") is necessary for the inactivation of photoactivated rhodopsin, the light receptor of the G-protein transduction cascade of rod photoreceptors. GRK1 has also been reported to be present in retinal cones in which its function is unknown. To examine the role of GRK1 in retinal cone signaling pathways, we measured in mice having null mutations of GRK1 (GRK1 /) cone-driven electroretinographic (ERG) responses, including an a-wave component identified as the field potential generated by suppression of the circulating current of the cone photoreceptors. Dark-adapted GRK1 / animals generated cone-driven ERGs having saturating amplitudes and sensitivities in both visible and UV spectral regions similar to those of wild-type (WT) mice. However, after exposure to a bright conditioning flash, the cone-driven ERGs of GRK1 / animals recovered 30-50 times more slowly than those of WT mice and similarly slower than the cone-driven ERGs of mice homozygously null for arrestin (Arrestin /), whose cone (but not rod) response recoveries were found to be as rapid as those of WT. Our observations argue that GRK1 is essential for normal deactivation of murine cone phototransduction and provide the first functional evidence for a major role of a specific GRK in the inactivation of vertebrate cone phototransduction.

Key words: G-protein coupled receptor; G-protein coupled receptor kinase; phototransduction; cone photoreceptors; photoresponse recovery kinetics; mouse genetics; electroretinography

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2062209-09$05.00/0

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