CALCIUM-DEPENDENT REGULATION OF CYCLIC-GMP PHOSPHODIESTERASE BY A PROTEIN FROM FROG RETINAL RODS

IN vertebrate photoreceptors, light reduces cyclic GMP concentration and closes cGMP-activated channels to induce a hyperpolarizing response 1. As Ca2+ can permeate the channels and the Na+ - CA2+ exchanger continuously extrudes Ca2+, closure of the channel results in a reduction of the inter-rod Ca2+ concentration 2-4. This is believed to be one of the mechanisms of light adaptation produced by activation of guanylate cyclase 5-9. Effects of Ca2+ on the cGMP phosphodiesterase (PDE) have been reported 10-15, but their physiological significance has remained unclear. We have perfused the inside-out preparation of a frog rod outer segment (I/O ROS (ref. 16), originally termed truncated ROS (ref. 17)), and find that Ca2+ in a physiological range regulates the light-activation of PDE. Therefore, PDE regulation by Ca2+ must be involved in light-adaptation in rods. The effect is mediated by a newly found protein which binds to disk membranes at high Ca2+ concentrations and prolongs PDE activation.