Mice lacking G-protein receptor kinase 1 have profoundly slowed recovery of cone-driven retinal responses

G-Protein receptor kinase 1 (GRK1) ("rhodopsin kinase") is necessary for th e inactivation of photoactivated rhodopsin, the light receptor of the G-pro tein transduction cascade of rod photoreceptors. GRK1 has also been reporte d to be present in retinal cones in which its function is unknown. To exami ne 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 pote ntial generated by suppression of the circulating current of the cone photo receptors. Dark-adapted GRK1 -/- animals generated cone-driven ERGs having saturating amplitudes and sensitivities in both visible and UV spectral reg ions similar to those of wild-type (WT) mice. However, after exposure to a bright conditioning flash, the cone-driven ERGs of GRK1 -/- animals recover ed 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 deact ivation of murine cone phototransduction and provide the first functional e vidence for a major role of a specific GRK in the inactivation of vertebrat e cone phototransduction.