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)
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004285:Dogs; D005260:Female; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D010713:Phosphatidylcholines; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000251:Adenosine Triphosphatases; C034688:sodium calcium ATPase; D002118:Calcium