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-mu-M 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 palmitolycarnitine 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.