Control of Lethal Arrhythmias Associated with Coronary Heart Disease. Calcium-Membrane Interactions.

摘要

The main purpose of this work was to study the role of calcium-membrane interactions in the genesis of lethal arrhythmias. Studies were directed in large part toward an understanding of some of the pharmacological and ionic controls of these interactions in a cardiac plasma membrane preparation developed and in sarcoplasmic reticulum (SR). Effects of local anesthetics,beta-adrenergic blockers,and ethanol on these membranes are described. The reaction mechanism of calcium transport by SR is described in terms of its kinetics and intermediate reactions. A calcium pump was reconstituted with virtually full recovery of calcium transport properties. Part of the work was directed toward an understanding of the effects of arrhythmogenic interventions,namely catecholamines. The authors have defined the mechanism of action of certain inotropic agents such as catecholamines that act to stimulate cyclic AMP production within the myocardium. Cyclic AMP activates protein kinase,which catalyzes the phosphorylation of a 22,000dalton protein. Increased phosphorylation of this protein is associated with increased calcium transport by cardiac SR. A possible relation of these effects of catecholamines to lethal arrhythmias is considered.