Calmodulin Modulation of Single Sarcoplasmic Reticulum Ca2+-release Channels from Cardiac and Skeletal Muscle

Sarcoplasmic reticulum (SR) contains a Ca2+-conducting channel that is believed to play a central role in excitation-contraction coupling by releasing the Ca2+ necessary for muscle contraction. The effects of calmodulin on single cardiac and skeletal muscle SR Ca2+-release channels were studied using the planar lipid bilayer-vesicle fusion technique. Calmodulin inhibited Ca2+-release channel opening by reducing the mean duration of single-channel open events without having an effect on single-channel conductance. Inhibition by calmodulin was dependent on Ca2+ concentration and occurred in the absence of ATP. The effects of calmodulin were reversed by mastoparan, a calmodulin-binding peptide. Two other calmodulin antagonists [calmidazolium and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] modified the gating behavior of the channel in the absence of exogenous calmodulin in a concentration- and Ca2+-dependent manner. Our results suggest that calmodulin can modulate excitation-contraction coupling by directly interacting with the SR Ca2+-release channel of cardiac and skeletal muscle.