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

• Published in: Biophysics (Oxford) 2008-12, Vol.53 (6), p.564-570
• Main Authors: Berezhnov, A. V., Fedotova, E. I., Nenov, M. N., Kokoz, Yu. M., Zinchenko, V. P., Dynnik, V. V.
• Format: Article
• Language: English
• Subjects: Biological and Medical Physics; Biophysics; Calcium; Cell Biophysics; Fatty acids; Heart; Physics; Physics and Astronomy; Rodents; Studies; Toxicity
• ISSN: 0006-3509; 1555-6654
• DOI: 10.1134/S0006350908060183

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 ([Ca 2+ ] i ) and caused cell death after a lag-period of 4–8 min. This effect was independent of extracellular calcium level and Ca 2+ inhibitors of L-type channels. Free myristic and palmitic acids at concentrations of 300–500 μM had little effect on [Ca 2+ ] 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 [Ca 2+ ] 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.