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.
Smith
J S
JS
Department of Biochemistry, School of Medicine, University of North Carolina, Chapel Hill 27599.
Rousseau
E
E
Meissner
G
G
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004285:Dogs; D007093:Imidazoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010455:Peptides; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014862:Wasp Venoms / Q000494:pharmacology
D015220:Calcium Channels; D002147:Calmodulin; D007093:Imidazoles; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D013449:Sulfonamides; D014862:Wasp Venoms; C031938:calmidazolium; C017967:W 7; C037500:mastoparan; D002118:Calcium