title: Acute ethanol treatment decreases intracellular calcium-ion transients in mouse single skeletal muscle fibres in vitro.
abstract: Alcohol misuse frequently leads to muscle weakness, which may also occur in the setting of acute and chronic alcoholic myopathies. At the cellular level, ethanol has been found to interfere with signalling mechanisms in cardiac myocytes, skeletal myotubes, and smooth muscle cells. In this study, we focused on the effects of ethanol on the intracellular calcium ([Ca(2+)](i)) transients responsible for excitation-contraction (EC) coupling in isolated mouse skeletal fibres loaded with the fluorescent Ca(2+) indicator fura-2. Following electrical stimulation, ethanol caused a significant reversible dose-dependent reduction in [Ca(2+)](i) transient amplitude, already significant at 100 mM ethanol (P = 0.03), without modifying resting [Ca(2+)](i). Evaluating the potential loci for the effects of ethanol, we indirectly measured sarcolemmal Ca(2+) entry by monitoring Mn(2+)-quenching of intracellular fura-2 via the nitrendipine-sensitive Ca(2+) channels during electrical pacing. Ethanol at doses of 20 mM and greater caused a dose-dependent reduction in the rate of fura-2 quenching (all at P<0.05). Moreover, the intracellular pool of Ca(2+) releasable by caffeine was found to be reduced at a minimum of 300 mM ethanol (P = 0.05). We conclude that ethanol reduces the [Ca(2+)](i) transients underlying EC coupling in single mouse skeletal muscle fibres. This acute effect of ethanol was primarily due to an inhibitory effect of ethanol on sarcolemmal Ca(2+) influx via voltage-operated Ca(2+)-channels and, to a lesser extent, to a reduction in the Ca(2+) sarcoplasmic reticulum loading state. This inhibitory effect of ethanol may be implicated in the development of muscle weakness with alcohol consumption.
authors.affiliation: Department of Internal Medicine, IDIBAPS, Hospital Clinic, Faculty of Medicine, University of Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cofán
authors.forename: J M
authors.initials: JM
authors.lastname: Nicolás
authors.forename: J
authors.initials: J
authors.lastname: Fernández-Solà
authors.forename: J
authors.initials: J
authors.lastname: Robert
authors.forename: E
authors.initials: E
authors.lastname: Tobías
authors.forename: E
authors.initials: E
authors.lastname: Sacanella
authors.forename: R
authors.initials: R
authors.lastname: Estruch
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Márquez
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D000431:Ethanol