Regulation of M-like K+ current, IKx, by Ca(2+)-dependent phosphorylation in rod photoreceptors.

An M-like K+ current (IKx) helps set the rod photoreceptor resting potential and accelerates the response to dim light. Recorded with ruptured-patch whole cell techniques, the amplitude of IKx diminished, and activation occurred at increasingly negative potentials as a function of time. In contrast, IKx was stable during nystatin perforated-patch recording. Stability during ruptured-patch recording could be induced by raising the intracellular Ca2+ concentration ([Ca2+]i) or by including caffeine or D-myo-inositol 1,4,5-trisphosphate in the pipette. This Ca(2+)-induced stability of IKx was blocked by inhibitors of Ca2+/calmodulin-dependent protein kinases, such as W-7, KN-62, chelerythrine, or H-7. Okadaic acid, an inhibitor of protein phosphatases, maintained IKx stability even at low [Ca2+]i. The requirement for phosphorylation was demonstrated by depleting MgATP or by providing 5'-adenylylimidophosphate, a nonhydrolyzable analog of ATP, either of which blocked the Ca(2+)-induced stability of IKx. These observations show that phosphorylation regulates IKx and that a stimulus controlling this action is [Ca2+]i. Should [Ca2+]i change during light adaptation, changes in IKx might alter the resting potential and temporal response properties of rod photoreceptors.