Calcium-dependent regulation of cyclic GMP phosphodiesterase by a protein from frog retinal rods

Abstract

INvertebrate photoreceptors, light reduces cyclic GMP concentration and closes cGMP-activated channels to induce a hyperpolarizing response1. 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+ concentration2–4. This is believed to be one of the mechanisms of light-adaptation produced by activation of guanylate cyclase5–9. Effects of Ca2+on the cGMP phosphodiesterase (PDE) have been reported10–15, 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.