Ca2-release channel gating and muscle contraction in a dose-depen-

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 Ca2 release from the sarcoplasmic reticulum (SR) in frog muscles. Acet-aldehyde 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 acetaldehyd