CALCIUM MODULATION OF LIGAND AFFINITY IN THE CYCLIC GMP-GATED ION CHANNELS OF CONE PHOTORECEPTORS

To investigate modulation of the activation of cGMP-gated loll channel s in cone photoreceptors, ive measured currents in membrane patches de tached from the outer segments of single cones isolated from striped b ass retina. The sensitivity of these channels to activation by cGMP de pends on the history of exposure to divalent cations of the membrane's cytoplasmic surface. In patches maintained in 20 mu M Ca++ and 100 mu M Mg++ after excision, the current amplitude dependence on cGMP is we ll described by a Hill equation with average values of K-1/2, the conc entration necessary to activate half the maximal current, of 86 mu M a nd a cooperativity index, n, of 2.57. Exposing the patch to a solution free of divalent cations irreversibly increases the cGMP sensitivity; the average value of K-1/2 shifts to 58.5 mu M and n shifts to 1.8. C hanges in cGMP sensitivity do not affect other functional parameters o f the ion channels, such as the interaction and permeation of mono-and divalent cations. Modulation of cGMP activation depends on the action of an endogenous factor that progressively dissociates from the chann el as Ca++ concentration is lowered below 1 mu M. The activity of the endogenous modulator is not well mimicked by exogenously added calmodu lin, although this protein competes with the endogenous modulator for a common binding site. Thus, the modulation of cGMP affinity in cones depends on the activity of an unidentified molecule that may not be ca lmodulin.