抄録
Acute intoxication due to alcohol consumption has been known to elicit reversible cardiac muscle dysfunction. Acetaldehyde (AcA), the major oxidized product of alcohol, may be a primary factor underlying alcohol-induced muscle dysfunction. We examined whether clinically relevant concentrations of AcA function as a primary toxin underlying muscle dysfunction, by measuring channel activity of rabbit purified ryanodine receptors (RyR2) with a lipid bilayer method and Ca2+ transient of rat single cardiac myocytes with a confocal imaging system. When applied to the RyR2 channel, AcA at one μM enhanced channel activity. AcA-induced channel activation was dose-dependent and was kept high even in presence of 300 μM AcA. Exposure of single myocytes to one μM AcA did not significantly affect parameters (resting intracellular Ca2+ level, time to peak, decay time) of Ca2+ transient elicited by single electrical field stimulation. However, AcA slowed decay time of Ca2+ transient on application of 2nd to 4th field stimulation and significantly retarded exponential decrement in amplitude of Ca2+ transient in respond to 2nd, 3rd and 4th field stimlation, in constant with a fast decrease in intact myocytes. These results suggest that AcA at clinical concentrations plays a role as the primary factor for alcohol-induced cardiac muscle dysfunction by modifing SR function. [Jpn J Physiol 55 Suppl:S90 (2005)]
