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⁺ 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.