Abstract
Lysophosphatidylcholine (LPC) has been reported to stimulate Na+-H+ exchange in rat cardiomyocytes. This action may be important in pathological conditions like ischemic injury where LPC is generated and Na+-H+ exchange activation is an important determinant of cardiac damage and dysfunction. It is unclear, however, if this stimulation of Na+-H+ exchange by LPC occurs through a direct action on the exchanger or through stimulation of a second messenger pathway. The purpose of the present investigation was to determine if lysolipids could directly affect Na+-H+ exchange. Purified cardiac sarcolemmal membranes were isolated and Na+-H+ exchange was measured by radioisotopic methods following addition of LPC. There were no effects of LPC on Na+-H+ exchange at LPC concentrations of ≤ 100 μM at all reaction times examined. Lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI) and lysoplasmenylcholine (LPEC) also did not alter Na+-H+ exchange at all concentrations and reaction times examined. We conclude that any stimulatory effects of lysolipids on Na+-H+ exchange do not occur through a direct action on the exchanger or its membrane lipid environment and must occur through a second messenger pathway.
Similar content being viewed by others
References
Chien KR, Han A, Sen A, Buja LM, Willerson JT: Accumulation of unesterified arachidonic acid in ischemic canine myocardium. Relationship to a phosphatidylcholine deacylation-reacylation cycle and the depletion of membrane phospholipids. Circ Res 54: 313-322, 1984
Saffitz JE, Corr PB, Lee BI, Gross RW, Williamson EK, Sobel BE: Pathophysiologic concentrations of lysophosphoglycerides quantified by electron microscopic autoradiography. Lab Invest 50: 278-286, 1984
Katz AM, Messineo FC: Lipid-membrane interactions and the pathogenesis of ischemic damage in the myocardium. Circ Res 48: 1-16, 1981
Prinzen FW, Van der Vusse GJ, Arts T, Roemen TH, Coumans WA, Reneman RS: Accumulation of nonesterified fatty acids in ischemic canine myocardium. Am J Physiol 247: H264-H272, 1984
Steenbergen C, Jennings RB: Relationship between lysophospholipid accumulation and plasma membrane injury during total in vitro ischemia in dog heart. J Mol Cell Cardiol 16: 605-621, 1984
Weglicki WB, Low MG: Phospholipases of the myocardium. Basic Res Cardiol 82: 107-112, 1987
Corr PB, Cain ME, Witkowski FX, Price DA, Sobel BE: Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides. Circ Res 44: 822-832, 1979
Arnsdorf MF, Sawicki GJ: The effects of lysophosphatidylcholine, a toxic metabolite of ischemia, on the components of cardiac excitability in sheep Purkinje fibers. Circ Res 49: 16-30, 1981
Pogwizd SM, Onufer JR, Kramer JB, Sobel BE, Corr PB: Induction of delayed after depolarizations and triggered activity in canine Purkinje fibers by lysophosphoglycerides. Circ Res 59: 416-426, 1986
Nakaya H, Tohse N: Electrophysiological effects of acetyl glyceryl ether phosphorylcholine on cardiac tissues: Comparison with lysophosphatidylcholine and long chain acyl carnitine. Br J Pharmacol 89: 749-757, 1986
Burnashev NA, Undrovinas AI, Fleidervish IA, Rosenshtraukh LV: Ischemic poison lysophosphatidylcholine modifies heart sodium channels gating inducing long-lasting bursts of openings. Pflügers Arch 415: 124-126, 1989
Undrovinas AI, Fleidervish IA, Makielski JC: Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine. Circ Res 71: 1231-1241, 1992
Sato T, Kiyosue T, Arita M: Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells. Pflügers Arch 420: 94-100, 1992
Kiyosue T, Arita M: Effects of lysophosphatidylcholine on resting potassium conductance of isolated guinea pig ventricular cells. Pflügers Arch 406: 296-302, 1986
Clarkson CW, Ten Eick RE: On the mechanism of lysophosphatidylcholine-induced depolarization of cat ventricular myocardium. Circ Res 52: 543-556, 1983
Karli JN, Karikas GA, Hatzipavlou PK, Levis GM, Moulopoulos SN: The inhibition of Na+ and K+ stimulated ATPase activity of rabbit and dog heart sarcolemma by lysophosphatidyl choline. Life Sci 24: 1869-1875, 1979
Pitts BJ, Okhuysen CH: Effects of palmitoyl carnitine and LPC on cardiac sarcolemmal Na+-K+-ATPase. Am J Physiol 247: H840-H846, 1984
Yamaguchi S, Tamagawa M, Nakajima N, Nakaya H: Selective impairment of HCO3(−)-dependent pHi regulation by lysophosphatidyl-choline in guinea pig ventricular myocardium. Cardiovasc Res 37: 179-186, 1998
Hoque AN, Haist JV, Karmazyn M: Na+-H+ exchange inhibition protects against mechanical, ultrastructural, and biochemical impairment induced by low concentrations of lysophosphatidylcholine in isolated rat hearts. Circ Res 80: 95-102, 1997
Meng HP, Pierce GN: Protective effects of 5-(N,N-dimethyl)amiloride on ischemia-reperfusion injury in hearts. Am J Physiol 258: H1615-H1619, 1990
Pierce GN, Czubryt MP: The contribution of ionic imbalance to ischemia/reperfusion-induced injury. J Mol Cell Cardiol 27: 53-63, 1995
Demareux N, Romanek R, Orlowski J, Grinstein S: ATP dependence of Na+-H+ exchange: Nucleotide specificity and assessment of the role of phospholipids. J Gen Physiol 109: 117-128, 1997
Goel DP, Vecchini A, Panagia V, Pierce GN: Altered cardiac Na+/H+ exchange in phospholipase D-treated sarcolemmal vesicles. Am J Physiol 279: H1179-H1184, 2000
Goel DP, Maddaford TG, Pierce GN: The effects of omega-3 polyunsaturated fatty acids on cardiac sarcolemmal Na+-H+ exchange. Am J Physiol 283: H1688-H1694, 2002
Williams SD, Ford DA: Activation of myocardial cAMP-dependent protein kinase by lysoplasmenylcholine. FEBS Lett 420: 33-38, 1997
Pierce GN, Panagia V: Role of phosphatidylinositol in cardiac sarcolemmal membrane sodium-calcium exchange. J Biol Chem 264: 15344-15350, 1989
Pierce GN, Philipson KD: Na+-H+ exchange in cardiac sarcolemmal vesicles. Biochim Biophys Acta 818: 109-116, 1985
Pierce GN, Ramjiawan B, Dhalla NS, Ferrari R: Na+-H+ exchange in cardiac sarcolemmal vesicles isolated from diabetic rats. Am J Physiol 258: H255-H261, 1990
Golfman LHT, Netticadan T, Panagia V, Dhalla NS: Modification of cardiac sarcolemmal Na+-Ca2+ exchange by lysophosphatidylcholine and palmitoylcarnitine. Cardiovasc Pathobiol 2: 181-185, 1998
Oishi K, Zheng B, Kuo JF: Inhibition of Na,K-ATPase and sodium pump by protein kinase C regulators sphingosine, lysophosphatidylcholine, and oleic acid. J Biol Chem. 265: 70-75, 1990
Eddlestone GT: ATP-sensitive K channel modulation by products of PLA2 action in the insulin-secreting HIT cell line. Am J Physiol 268: C181-C190, 1995
Subbaiah PV, Chen CH, Bagdade JD, Albers JJ: Substrate specificity of plasma lysolecithin acyltransferase and the molecular species of lecithin formed by the reaction. J Biol Chem 260: 5308-5314, 1985
Rabini RA, Galassi R, Fumelli P, Dousset N, Solera ML, Valdiguie P, Curatola G, Ferretti G, Taus M, Mazzanti L: Reduced Na+-K+-ATPase activity and plasma lysophosphatidylcholine concentrations in diabetic patients. Diabetes 43: 915-919, 1994
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goel, D.P., Ford, D.A. & Pierce, G.N. Lysophospholipids do not directly modulate Na+-H+ exchange. Mol Cell Biochem 251, 3–7 (2003). https://doi.org/10.1023/A:1025444824624
Issue Date:
DOI: https://doi.org/10.1023/A:1025444824624