Acetaldehyde alters Ca -release channel gating and muscle contraction in a dose-dependent manner

Oba, Toshiharu, and Yoshitaka Maeno. Acetaldehyde alters Ca -release channel gating and muscle contraction in a dose-dependent manner. Am J Physiol Cell Physiol 286: C1188–C1194, 2004. First published December 30, 2003; 10.1152/ajpcell.00388.2003.— We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to 50–200 M acetaldehyde enhanced channel activity of frog RyR and rabbit RyR1 incorporated into lipid bilayers. An increase in acetaldehyde to 1 mM modified channel activity in a time-dependent manner, with a brief activation and then inhibition. Application of 200 M acetaldehyde to frog fibers increased twitch tension. The maximum rate of rise of tetanus tension was accelerated to 1.5 and 1.74 times the control rate on exposure of fibers to 50 and 200 M acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200–400 M acetaldehyde induced Ca release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by 12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca release from the SR by increasing the open probability of the RyR channel, resulting in increased tension. However, the effects of acetaldehyde at clinical doses (1–30 M) are unlikely to mediate alcohol-induced acute muscle dysfunction.