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Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids

  • Cell Biophysics
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Abstract

By means of fluorescent microscopy, long-chain fatty acid derivatives, myristoylcarnitine and palmitoylcarnitine, were shown to exert the most toxic effect on rat ventricular cardiomyocytes. The addition of 20–50 μM acylcarnitines increased calcium concentration in cytoplasm ([Ca2+]i) and caused cell death after a lag-period of 4–8 min. This effect was independent of extracellular calcium level and Ca2+ inhibitors of L-type channels. Free myristic and palmitic acids at concentrations of 300–500 μM had little effect on [Ca2+]i within 30 min. We suggest that the toxic effect is due to the activation of calcium channels of sarcoplasmic reticulum by acylcarnitines and/or arising acyl-CoA. Mitochondria play a role of calcium-buffer system under these conditions. The calcium capacity of the buffer determines the duration of the lag-period. Phosphate increases the calcium capacity of mitochondria 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 mitochondria 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.

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Abbreviations

FA:

fatty acids

MPP:

mitochondrial permeable pore

MC:

myristoylcarnitine

PC:

palmitoylcarnitine

RyR:

ryanodine channels

IP3R:

IP3-sensitive channels

SR:

sarcoplasmic reticulum

SERCA:

sarcoplasmic/endoplasmic reticulum Ca2+-ATPase

PMCA:

plasma membrane Ca2+-ATPase

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Authors and Affiliations

  1. Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290, Russia

    A. V. Berezhnov, E. I. Fedotova & V. P. Zinchenko

  2. Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, 142290, Russia

    M. N. Nenov, Yu. M. Kokoz & V. V. Dynnik

Authors
  1. A. V. Berezhnov
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  2. E. I. Fedotova
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  3. M. N. Nenov
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  4. Yu. M. Kokoz
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  5. V. P. Zinchenko
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  6. V. V. Dynnik
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Original Russian Text © A.V. Berezhnov, E.I. Fedotova, M.N. Nenov, Yu.M. Kokoz, V.P. Zinchenko, V.V. Dynnik, 2008, published in Biofizika, 2008, Vol. 53, No. 6, pp. 1025–1032.

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Berezhnov, A.V., Fedotova, E.I., Nenov, M.N. et al. Destabilization of the cytosolic calcium level and the death of cardiomyocytes in the presence of derivatives of long-chain fatty acids. BIOPHYSICS 53, 564–570 (2008). https://doi.org/10.1134/S0006350908060183

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  • DOI: https://doi.org/10.1134/S0006350908060183

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