Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives

A. V. Berezhnov, E. I. Fedotova, M. N. Nenov, I. M. Kokoz, V. P. Zinchenko, V. V. Dynnik

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5 Scopus citations

Abstract

It has been shown using the fluorescent microscopy technique that long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, exert the most toxic effect on rat ventricular cardiomyoctes. The addition of 20-50 microM acylcarnitines increases calcium concentration in cytoplasm ([Ca2+]i) and causes cell death after the 4-8 min lag-period. This effect is independent on extracellular calcium and L-type calcium channel inhibitors. Free acids (myristic and palmitic acids) at a concentration of 300-500 microM have a little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of sarcoplasmic reticulum calcium channels by acylcarnitines and resulting acyl-CoA. Mitochondria play a role of calcium-buffer system in these conditions. The calcium capacity of this buffer determines the lag-period. Phosphate increases the calcium capacity of mitochondrial and the lag-period. In the presence of rotenone and oligomycin the elevation of [Ca2+]i after the addition of acylcarnitines occurs without the lag-period. The exhaustion of the mitochondrial calcium-buffer capacity or significant depolarization of mitochondrial leads to a rapid release of calcium from mitochondria and cell death. Thus, the activation of reticular calcium channels is the main reason of the toxicity of myristoylcarnitine and palmitoylcarnitine.

Original languageEnglish (US)
Pages (from-to)1025-1032
Number of pages8
JournalBiofizika
Volume53
Issue number6
StatePublished - Nov 1 2008

ASJC Scopus subject areas

  • Medicine(all)

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    Berezhnov, A. V., Fedotova, E. I., Nenov, M. N., Kokoz, I. M., Zinchenko, V. P., & Dynnik, V. V. (2008). Destabilization of the cytosolic calcium level and cardiomyocyte death in the presence of long-chain fatty acid derivatives. Biofizika, 53(6), 1025-1032.