Prolonged rod photoresponse and enhanced cone sensitivity in the transgenic mouse retina lacking arrestin and guanylate cyclase activating proteins

Abstract

Light activates visual pigments and downstream G protein signalling cascades in rod and cone photoreceptor cells. Timely response inactivation requires visual pigment inactivation by arrestin and restoration of cellular cGMP by guanylate cyclase activating proteins (GCAPs). Using GCAP‐deficient mice, we previously showed that apo‐opsin produces photoresponse‐like signals. To investigate the inactivation of apo‐opsin by arrestin, we generated GCAP‐deficient mice lacking arrestin ( Gcaps ^−/− Arr1 ^−/− ). Using ex vivo electroretinography, we found that the dim flash responses of Gcaps ^−/− Arr1 ^−/− rods were ∼100‐fold slower than those of control Gcaps ^−/− rods. As a result, even brief dim light exposure during sample preparation resulted in prolonged rod saturation, so that only cone responses were initially observed in Gcaps ^−/− Arr1 ^−/− retinas. In contrast, rod responses were observed immediately when Gcaps ^−/− Arr1 ^−/− retinas were dissected under infrared light to avoid rod photoactivation. Microspectrophotometry showed that the rate of production and decay of the active rhodopsin photoproduct, Meta II, was comparable between Gcaps ^−/− and Gcaps ^−/− Arr1 ^−/− rods. However, the rate of photoproduct Meta III decay was 3‐fold slower in Gcaps ^−/− Arr1 ^−/− rods, supporting a role for arrestin in accelerating the decay of photoactivated rhodopsin. To evaluate the effect of rod saturation on cone responses, we compared photopic cone responses from wild‐type and Gnat1 ^−/− retinas lacking rod signalling. Cone photoresponses were larger and more sensitive in wild‐type retinas, suggesting the potentiation of cone function by the saturation of rod phototransduction. Together, our results demonstrate that the very slow deactivation of rod responses in Gcaps ^−/− Arr1 ^−/− retinas might result in selective and potentiated cone signalling in darkness. image