Phospholipase D produces increased contractile force in rabbit ventricular muscle

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.