Ethanol delays and reverses lysophosphatidylcholine-induced calcium overload in neonatal rat heart cells

Abstract

Increased lysophosphatidylcholine (LPC) production by the ischemic heart is associated with tissue damage. In vitro, LPC produces an increase in cytosolic [Ca2+], usually followed by cell contracture and lysis. Since ethanol reportedly protect cells during ischemia-reperfusion, we wished to determine whether ethanol could protect heart cells against LPC-induced Ca2+ overload. Newborn rat heart cells in culture were loaded with Fura-2 and [Ca2+]i recorded in individual cells. The presence of 22 or 44 mM ethanol increased the time required for 10 microM x L-palmitoyl-LPC to produce maximal Ca2+ accumulation from 8.4+/-0.4 min (n=47) to 21.1+/-2.1 x min (n=32; P<0.01) and 23.8+/-1.8 min (n=10; P<0.01) respectively. The onset of the [Ca2+]i increase could be reversed partially by the addition of ethanol (44 or 88 mM). After the addition of 22 mM ethanol, the cells retained the Fura-2 three times longer than under control conditions. Ethanol (88 mM) decreased the critical micelle concentration of LPC, thus decreasing the LPC monomer concentration in this solution. La3+ also protected the cells against LPC but no further protection was afforded by the addition of ethanol. Our results suggest that ethanol concentrations commonly found in the blood of social drinkers protect heart cells against the deleterious effect of LPC.

Ethanol protects against lysophosphatidylcholine-induced uncoupling of cardiac cell pairs

“…Although we cannot conclude from our results that LPCinduced uncoupling is mediated by calcium overload, both phenomenon present similarities: the delay for total uncoupling in the presence of LPC is consistent with the time required to reach a stable elevated [Ca 2+ ] plateau, and I Ca,L inhibitors (nisoldipine in the [Ca 2+ ] measurement experiments [14] and Cd 2+ , present in the external solution in all experiments in the present study) did not affect LPC-mediated calcium overload or cell uncoupling. The interaction between ethanol and LPC could occur at the membrane level, the physical state of the LPC micelles or Ca 2+ entry mechanisms [14].…”

“…We previously documented that LPC induces calcium overload in cardiac myocytes which is dependent on the presence of calcium in the extracellular medium [14]. Although we cannot conclude from our results that LPCinduced uncoupling is mediated by calcium overload, both phenomenon present similarities: the delay for total uncoupling in the presence of LPC is consistent with the time required to reach a stable elevated [Ca 2+ ] plateau, and I Ca,L inhibitors (nisoldipine in the [Ca 2+ ] measurement experiments [14] and Cd 2+ , present in the external solution in all experiments in the present study) did not affect LPC-mediated calcium overload or cell uncoupling.…”

“…We have also shown that ethanol postpones LPC-induced calcium overload [14]. The objective of the present study was therefore to assess if ethanol could afford protective effects against LPC-induced uncoupling in cardiac myocytes.…”

“…We have recently demonstrated that LPC, at concentrations measured during cardiac ischemia (i.e., 5-50 mol·l -1 ), inhibits intercellular coupling [9] and induces an intracellular calcium overload [14]. We have also shown that ethanol postpones LPC-induced calcium overload [14].…”

Ischemic, genetic and pharmacological origins of cardiac arrhythmias: The contribution of the Quebec Heart Institute

“…We then performed complementary experiments using the fura-2 fluorescence technique to assess LPC and ethanol effects on the intracellular calcium dynamics in cardiac myocytes (80). We demonstrated that ethanol was able to delay and reverse LPCinduced calcium overload, an indicator of cell injury.…”