Ethanol Acutely Decreases Calcium Transients in Cultured Human Myotubes

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+]i) 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.

A low dose of alcohol does not impact skeletal muscle performance after exercise-induced muscle damage

“…Comparable doses to those used in our previous work have been found to decrease calcium transients (Nicolas et al 1998) as well as negatively impacting the regulation of a number of chemokines (Szabo et al 1999). Separately, a humoral effect, importantly on the androgens, has also been previously described (Vingren et al 2003).…”

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“…This increase in myocardium apoptosis is a reflection of a common pathogenic mechanism inducing progressive heart damage, independently of the origin of the damaging agent . In alcoholics, myocardium apoptosis does not only depend on ethanol consumption but also to the presence of structural heart damage (Ferna´ndez-Solaè t al., 2006;Ja¨nka¨la¨et al, 2002), demonstrating that myocardium apoptosis is a complex mechanism related not only to the original trigger agent but also to intermediate causes of myocardial damage that activate mechanisms of cell lesion such as mitochondrial caspases, disturbances in intracellular cell transients (Nicola´s et al, 1998), protein synthesis (Ferna´ndez-Sola`et al, 2007), or oxidative damage (Fatjoé t al., 2005). Myostatin activity has been reported to protect myocardium cells from apoptosis (Joulia-Ekaza and Cabello, 2006).…”

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“…Firstly, alcohol inhibits Ca 2+ transients into the myocyte by inhibiting sarcolemmal Ca 2+ channel actions. This action is reported in isolated human myotubes and rodent muscle tubes in-vitro [10,11,12]. Consequently this will impair excitation-contraction coupling, decreasing strength output.…”