RGS9-1 is required for normal inactivation of mouse cone phototransduction

[摘要] Purpose: To test the hypothesis that Regulator of G-proteinSignaling 9 (RGS9-1) is necessary for the normal inactivation of retinalcones.Methods: Mice having the gene RGS9-1 inactivated in both alleles(RGS9-1 -/-) were tested between the ages 8-10 weeks withelectroretinographic (ERG) protocols that isolate cone-driven responses.Immunohistochemistry was performed with a primary antibody againstRGS9-1 (anti-RGS9-1c), with the secondary conjugated to fluoresceinisothiocyanate, and with rhodamine-conjugated peanut agglutinin.Results: (1) Immunohistochemistry showed RGS9-1 to be stronglyexpressed in the cones of wildtype (WT is C57BL/6) mice, but absent fromthe cones of RGS9-1 mice. (2) Cone-driven b-wave responses ofdark-adapted RGS9-1 -/- mice had saturating amplitudes and sensitivitiesin the midwave and UV regions of the spectrum equal to or slightlygreater than those of WT (C57BL/6) mice. (3) Cone-driven b-wave anda-wave responses of RGS9-1 -/- mice recovered much more slowly thanthose of WT after a strong conditioning flash: for a flash estimated toisomerize 1.2% of the M-cone pigment and 0.9% of the UV-cone pigment,recovery of 50% saturating amplitude was approximately 60-fold slowerthan in WT.Conclusions: (1) The amplitudes and sensitivities of the cone-drivenresponses indicate that cones and cone-driven neurons in RGS9-1 -/- micehave normal generator currents. (2) The greatly retarded recovery ofcone-driven responses of RGS9-1 -/- mice relative to those of WT miceestablishes that RGS9-1 is required for normal inactivation of the conephototransduction cascades of both UV- and M-cones.

[学科分类] 生物化学/生物物理