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Effects of some L-carnitine derivatives on heart membrane ATPases

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Summary

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 μM 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 palmitoly-carnitine 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.

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Authors and Affiliations

  1. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada

    Naranjan S. Dhalla, František Kolár & Kanu R. Shah

  2. Department of Physiology, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla, František Kolár & Kanu R. Shah

  3. Department of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla, František Kolár & Kanu R. Shah

  4. Cattedra de Cardiologia, University of Brescia, Brescia, Italy

    Roberto Ferrari

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  1. Naranjan S. Dhalla
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  2. František Kolár
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  3. Kanu R. Shah
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  4. Roberto Ferrari
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Dhalla, N.S., Kolár, F., Shah, K.R. et al. Effects of some L-carnitine derivatives on heart membrane ATPases. Cardiovasc Drug Ther 5, 25–30 (1991). https://doi.org/10.1007/BF00128240

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