Removal of Mg2+ inhibition of cardiac ryanodine receptor by palmitoyl coenzyme A.
45Ca2+ fluxes and planar bilayer recordings indicated that the fatty acid metabolite palmitoyl coenzyme A, but not free coenzyme A or palmitic acid, stimulated the cardiac ryanodine receptor channel of pig heart sarcoplasmic reticulum. Palmitoyl CoA reactivated channels inhibited by concentrations of cytoplasmic free Mg2+ in the physiological range. Reactivation by palmitoyl CoA in the presence of Mg2+ was stimulated by myoplasmic free Ca2+ in the micromolar range. Acyl coenzyme A derivatives may be utilized by cardiac muscle cells to compensate for the severe Mg2+ inhibition of ryanodine receptors which would otherwise leave Ca2+ stores unresponsive to Ca2+ and to other cytosolic ligands involved in signal transduction.
Connelly
T
T
Department of Anesthesiology, University of Wisconsin School of Medicine, Madison 53706.
Ahern
C
C
Sukhareva
M
M
Coronado
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D007700:Kinetics; D008051:Lipid Bilayers; D008274:Magnesium / Q000494:pharmacology*; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010171:Palmitoyl Coenzyme A / Q000494:pharmacology*; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D013552:Swine; D013997:Time Factors
D015220:Calcium Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D010171:Palmitoyl Coenzyme A; D008274:Magnesium; D002118:Calcium