Ethanol acutely decreases calcium transients in cultured human myotubes

Josep M. Nicolás, Emilia Antúnez, Andrew P. Thomas, Joaquim Fernández-Solà, Ester Tobías, Ramón Estruch, Alvaro Urbano-Márquez

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34 Scopus citations

Abstract

Ethanol consumption frequently leads to a number of skeletal muscle disorders, including acute and chronic alcoholic myopathy. Ethanol has been found to interfere with signal transduction mechanisms in cardiac and smooth muscle cells. We studied the effects of ethanol on the intracellular calcium ([Ca2+]) transients responsible for excitation-contraction coupling in human myotubes from chronic alcoholic patients and healthy controls. Cultured myotubes were loaded with the fluorescent Ca2+ indicator fura-2 and evaluated on a single-cell basis. Following electrical stimulation, ethanol caused a significant reversible dose-dependent reduction in [Ca2+](i) transient amplitude, achieving a mean decrease of 36 ± 5% at 300 mM ethanol (p < 0.01), without modifying the basal [Ca2+](i). This acute effect of ethanol was similar in myotubes obtained from chronic alcoholics and controls. Similarly, ethanol caused a dose-dependent reduction of [Ca2+](i) transient amplitude in control samples when depolarization was elicited by 100 mM KCl (p < 0.01). Several potential mechanisms of ethanol action were studied in control muscle samples. Sarcolemmal Ca2+ entry was measured indirectly by monitoring Mn2+-quenching of intracellular fura-2 via the nitrendipine-sensitive Ca2+ channels during electrical pacing. Ethanol at doses of 100 mM and greater caused a dose-dependent reduction in the rate of quench (p < 0.01). In addition, the intracellular pool of Ca2+ releasable by Caffeine was found to be reduced at 300 mM ethanol (p < 0.05). We conclude that ethanol reduces the [Ca2+](i) transients underlying excitation- contraction coupling in human myotubes, and that this occurs to a similar extent in cells obtained from chronic alcoholics and controls. This acute effect of ethanol was primarily due to an inhibitory effect of ethanol on sarcolemmal Ca2+ influx via voltage-operated Ca2+ channels, although there may also be an effect on the Ca2+ sarcoplasmic reticulum loading state.

Original languageEnglish (US)
Pages (from-to)1086-1092
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume22
Issue number5
DOIs
StatePublished - Aug 1998
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Keywords

  • Calcium
  • Ethanol
  • Excitation-Contraction Coupling
  • Myotubes

Cite this

Nicolás, J. M., Antúnez, E., Thomas, A. P., Fernández-Solà, J., Tobías, E., Estruch, R., & Urbano-Márquez, A. (1998). Ethanol acutely decreases calcium transients in cultured human myotubes. Alcoholism: Clinical and Experimental Research, 22(5), 1086-1092. https://doi.org/10.1111/j.1530-0277.1998.tb03705.x