Effects of some L-carnitine derivatives on heart membrane ATPases.
In order to understand the role of carnitine metabolites in the genesis of cellular dysfunction and damage due to myocardial ischemia, the effects of 1-100 microM L-carnitine, acetylcarnitine, propionylcarnitine, and palmitoylcarnitine were investigated on rat heart sarcolemmal, sarcoplasmic reticular, and mitochondrial ATPase activities. Palmitoylcarnitine, unlike acetylcarnitine, propionylcarnitine and carnitine, produced marked inhibitory actions on sarcolemmal Na,K-ATPase and Ca2(+)-stimulated ATPase, as well as sarcoplasmic reticular Ca2(+)-stimulated ATPase activities; Na,K-ATPase was most sensitive. Although palmitoylcarnitine, unlike carnitine or its short-chain fatty-acid derivatives, also depressed sarcolemmal Ca2+ ATPase or Mg2+ ATPase, sarcoplasmic reticular Mg2+ ATPase, and mitochondrial Mg2+ ATPase, mitochondria were less sensitive in comparison to other organelles. Myofibrillar Ca2(+)-stimulated ATPase was slightly inhibited by very high concentrations of palmitoylcarnitine only. It is suggested that the observed depression of the sarcolemmal Na(+)-pump system by low concentrations of long-chain acyl derivatives of carnitine may contribute towards the pathogenesis of arrhythmias due to myocardial ischemia. Furthermore, the inhibition of Ca2(+)-pump mechanisms in the sarcolemmal and sarcoplasmic reticular membranes by relatively high concentrations of palmitoylcarnitine may result in the occurrence of intracellular Ca2+ overload and subsequent cell damage, as well as cardiac dysfunction due to myocardial ischemia.
Dhalla
N S
NS
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Kolár
F
F
Shah
K R
KR
Ferrari
R
R
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D008297:Male; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism
C003223:propionylcarnitine; D000108:Acetylcarnitine; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002331:Carnitine