Altered cardiac Na(+)/H(+) exchange in phospholipase D-treated sarcolemmal vesicles.
Cardiac sarcolemmal Na(+)/H(+) exchange is critical for the regulation of intracellular pH, and its activity contributes to ischemia-reperfusion injury. It has been suggested that the membrane phospholipid environment does not modulate Na(+)/H(+) exchange. The present study was carried out to determine the effects on Na(+)/H(+) exchange of modifying the endogenous membrane phospholipids through the addition of exogenous phospholipase D. Incubation of 0.825 U of phospholipase D with 1 mg of porcine cardiac sarcolemmal vesicles hydrolyzed 34 +/- 2% of the sarcolemmal phosphatidylcholine and increased phosphatidic acid 10.2 +/- 0.5-fold. Treatment of vesicles with phospholipase D resulted in a 46 +/- 2% inhibition of Na(+)/H(+) exchange. Na(+)/H(+) exchange was measured as a function of reaction time, extravesicular pH, and extravesicular Na(+). All of these parameters of Na(+)/H(+) exchange were inhibited following phospholipase D treatment compared with untreated controls. Passive efflux of Na(+) was unaffected. Treatment of sarcolemmal vesicles with phospholipase C had no effect on Na(+)/H(+) exchange. We conclude that phospholipase D-induced changes in the cardiac sarcolemmal membrane phospholipid environment alter Na(+)/H(+) exchange.
Goel
D P
DP
Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada R2H 2A6.
Vecchini
A
A
Panagia
V
V
Pierce
G N
GN
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology*; D008563:Membrane Lipids / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D015388:Organelles / Q000187:drug effects / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010713:Phosphatidylcholines / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism* / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013552:Swine
D008563:Membrane Lipids; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; D010743:Phospholipids; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D012964:Sodium; D010739:Phospholipase D