Modulation of the cGMP-gated channel of rod photoreceptor cells by calmodulin

Abstract

PHOTOBLEACHING of rhodopsin in rod photoreceptors activates the visual cascade system leading to a decrease in cyclic GMP and the closure of cGMP-gated channels in the rod outer segment plasma membrane^1–4. Calcium plays an important role in the recovery of the rod outer segment to its dark state by regulating the resynthesis of cGMP by guanylate cyclase^5–7. Here we report that calmodulin, a Ca²⁺-binding protein present in the rod outer segment^8,9, increases the apparent Michaelis constant of the channel for cGMP. This results in a decrease in the rate of cation influx into the rod outer segment by two- to sixfold at low cGMP concentrations and has the effect of increasing the sensitivity of the channel to small changes in cGMP levels during phototrans-duction. Biochemical studies indicate that calcium–calmodulin binds to a protein of M_r 240K which is tightly associated with the channel¹⁰. On the basis of these studies, Ca²⁺ is suggested to play a central role in photorecovery and light adaptation, not only by regulating guanylate cyclase, possibly through recoverin^6,7, but also by modulating the cGMP-gated channel through calmodulin interaction with the 240K protein.