AJP - Heart and Circulatory Physiology, Vol 247, Issue 5 880-H885, Copyright © 1984 by American Physiological Society
Phospholipase D increases cell surface Ca2+ binding and positive inotropy in rat heart
J. M. Burt, T. L. Rich and G. A. Langer
An increase in the content of anionic phospholipid (AP) in the sarcolemma
may lead to increased Ca2+ binding and a concomitant inotropic response. To
test this hypothesis we treated cultured neonatal rat myocardial cells with
phospholipase D (PLD), an enzyme that converts membrane phospholipids to
phosphatidic acid. PLD treatment resulted in an increase in total
exchangeable Ca2+ of 36%, or 1.56 +/- 0.27 mmol Ca2+/kg dry wt, 79 +/- 3%
of which remained displaceable by La3+. The quantity of Ca2+ displaced by
polymyxin B, a drug that displaces Ca2+ preferentially from anionic
phospholipid sites, increased by 85% from a predicted 0.74 +/- 0.07 to 1.37
+/- 0.19 mmol Ca2+/kg dry wt. Simultaneously the contractility of neonatal
rat ventricular tissue increased by 1.7- to 2.5-fold. Spontaneous
electrical activity of treated cells was not significantly altered. Thus
PLD treatment, which increases the quantity of AP in the membrane, resulted
in an 85% increase in Ca2+ bound to AP and concomitantly resulted in a
significant increase in contractility. Present results, in association with
published results on the effect of PLD on Na+-Ca2+ exchange (J. Biol. Chem.
259: 16-19, 1984), indicate that Ca2+ bound to anionic sarcolemmal
phospholipids plays a major role in the control of transsarcolemmal Ca2+
flux and force development.
