Mechanisms of endotoxin-induced impairment in Na+-Ca2+ exchange in canine myocardium.

Effects of endotoxin administration on the Na+-Ca2+ exchange in canine cardiac sarcolemma were characterized. In addition, roles of phospholipase A2 and phosphorylation on the endotoxin-induced impairment in Na+-Ca2+ exchange were investigated. The results show that intravesicular sodium (Nai+)-dependent 45Ca2+ uptake was decreased by 39-66% (P less than 0.05) and extravesicular sodium (Nao+)-induced 45Ca2+ efflux was decreased by 36-52% (P less than 0.05) at 2 h following endotoxin administration. Ca2+o-induced 45Ca2+ efflux in the absence of Ko+ was not affected, but Ca2+o-induced 45Ca2+ efflux in the presence of Ko+ was significantly reduced by endotoxin administration. The stoichiometry of Na+-Ca2+ exchange was altered from 3 Na+ for 1 Ca2+ for the control to 2 Na+ for 1 Ca2+ for the endotoxin-treated dogs. The ATP-dependent 22Na+ uptake and Na+-Ca2+ exchange in inside-out vesicles remained unchanged after endotoxin injection. Digestion of control heart sarcolemmal vesicles with exogenous phospholipase A2 (0.02-0.06 unit/500 micrograms protein) inhibited Na+-Ca2+ exchange activity measured as Nai+-dependent 45Ca2+ uptake, and the inhibition was concentration dependent. Lysophosphatidylcholine addition to the control cardiac sarcolemma had no effect on Na+-Ca2+ exchange. The inhibition of Na+-Ca2+ exchange caused by phospholipase A2 digestion in the control heart sarcolemma was completely reversible by the addition of phosphatidylcholine (0.1 mM). The inhibition of Na+-Ca2+ exchange caused by the in vivo administration of endotoxin was completely reversible by the addition of phosphatidylcholine (0.1-0.15 mM).(ABSTRACT TRUNCATED AT 250 WORDS)