Role of sarcolemmal-bound calcium in regulation of myocardial contractile force

Abstract

A rapidly exchangeable component of cellular calcium plays a significant role in the control of force development in heart muscle. Recently completed studies indicate that a large fraction of this calcium is bound to sites on the sarcolemma: The curve that relates extracellular calcium ([Ca]0)(from 50 microM to 10 mM) to force development and the one that relates [Ca]0 to calcium bound to a highly purified sarcolemmal fraction are superimposable. The ability of a series of cations (lanthanum, cadmium, manganese, magnesium) to uncouple excitation from contraction is the same as their relative ability to displace calcium from sarcolemma. Polymyxin B, a highly charged cationic amphiphilic peptidolipid, specifically competes for calcium-binding sites on anionic and zwitterionic phospholipid. It is a potent displacer of calcium from myocardial cells and purified sarcolemma and a potent uncoupler. Phospholipase D cleaves the nitrogenous base from sarcolemmal phospholipid with production of anionic phosphatidic acid. Phospholipase D treatment increases calcium bound to cells and to purified sarcolemma and increases force development of ventricular tissue from both neonatal rats and adult rabbits. Insertion of charged amphiphiles in the sarcolemma as phospholipid analogues modulates interaction of calcium with myocardial sarcolemma. Anionic dodecylsulfate increases calcium bound to sarcolemmal vesicles by more than 80% and increases force development in rabbit papillary muscle by 100%. Cationic dodecyltrimethylamine produces a negative effect on binding and decreases contractile force by 70%. Neutral laurylacetate produces negligible effects on binding and force development. The effect of pH variation on calcium binding to phospholipid extracted from sarcolemma indicates that the latter accounts for at least 75% of the binding.(ABSTRACT TRUNCATED AT 250 WORDS)