MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.
Visual opsins maintain a weak, constitutive activity that can be modulated pharmacologically. Retinoids, including the truncated analog, b-ionone, increase the activity of opsins of rods and the opsins of all cones except the red-sensitive one. The ability of b-ionone and several other retinoids to slow pigment regeneration by competing with 11-cis retinal suggested that activation was effected at the chromophore binding pocket. However, some retinoids, such as all trans retinal activate opsin but do not slow the rate of pigment regeneration. Furthermore, we have shown by single cell recording that b-ionone elicit a response in dark adapted blue-sensitive rods and cones by activating their visual pigment, in which the chromophore binding pocket is already occupied. However, in a reconstituted system, heterologously expressed blue-sensitive cone/rod opsin (the same opsin is expressed in both cell types) failed to show an increase in activity in the presence of b-ionone. One difference in the two kinds of experiments is that the reconstituted pigment was regenerated with 11-cis retinal (A1) while the native pigment in our recodings is predominantly 3-dehydro, 11-cis retinal (A2). We propose to test whether chromophore type accounts for the different behavior by recording the electrical responses of single blue-sensitive rods to b-ionone before and after replacing the native A2 chromophore with A1. These studies may reveal an important evolutionary constraint that determined which chromophore came into use by a particular species.