Phospholipase D produces increased contractile force in rabbit ventricular muscle.

Abstract

SUMMARY. Inclusion of phospholipase D (Streptomyces chromofuscus, 5 U/ml) in the medium perfusing rabbit papillary muscles increased peak force development by 78% and peak dF/dt by 89%. The maximal contractile response occurred 40-50 minutes after addition of the enzyme to the perfusate. As peak contractile response developed, aftercontractions appeared in most muscles. The inotropic response was slowly reversible, with disappearance of aftercontractions, upon discontinuation of the enzyme. Phospholipase D produces a specific increase of phosphatidic acid in the sarcolemma and, therefore, an increase in net anionic charge on the membrane. It has been shown previously that phospholipase D induces a large increase in sarcolemmal calcium binding. We propose, on the basis of the present study, that phospholipid-bound calcium may play a significant role in the control of contractile force in mammalian myocardium. (Circ Res 56: 146-149, 1985)

Expression of phospholipase D isozymes in scar and viable tissue in congestive heart failure due to myocardial infarction

“…A role for SL PLD and its hydrolytic product, PA, in cardiac function has been indicated in a number of studies [27][28][29][30]. For example, the cardiac SL Na + -Ca 2+ exchanger activity has been shown to be increased with the treatment of the membranes with exogenous PLD [28].…”

“…For example, the cardiac SL Na + -Ca 2+ exchanger activity has been shown to be increased with the treatment of the membranes with exogenous PLD [28]. Such a treatment has also been shown to increase Ca 2+ -binding and force of contraction of the heart [29]. The observation that exogenous addition of PA or PLD generates Ca 2+ -dependent slow action potentials in depolarized rat atrium supports the role of PA in mediating the increase of Ca 2+ influx into the cardiac cells [30].…”

The effect of pH on cellular and membrane calcium binding and contraction of myocardium. A possible role for sarcolemmal phospholipid in EC coupling.

“…(4) Phospholipase D (PLD) cleaves the nitrogenous base from sarcolemmal phospholipids with the production of anionic phospharidic acid. PLD treatment increases Ca ++ bound to whole, cells (Burt et al, 1984) and to purified sarcolemma (Langer and Nudd, 1983) and increases force development of ventricular tissue from both neonatal rat (Burt et al, 1984) and adult rabbit (Langer and Rich, 1985) by 80-150%. (5) Finally, charged amphiphiles, used as phospholipid analogues, modulate interaction of calcium with myocardial sarcolemma (Philipson et al, 1984).…”

Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes.

“…For example, exogenous phospholipase D increased the contractility of neonatal rat ventricular tissue35 and produced positive inotropy in rabbit papillary muscle. 36 Philipson and Nishimoto'6 demonstrated that exogenous phospholipase D stimulated Na+-Ca2' exchange in cardiac sarcolemmal vesicles, which was accompanied by an increase of phosphatidic acid in the sarcolemma. Depending on the intracellular and extracellular Na+ and Ca21 concentrations and the membrane potential, this bidirectional transport mechanism could elevate cytosolic calcium and thereby increase contractility.…”