title: Acetaldehyde alters Ca2+-release channel gating and muscle contraction in a dose-dependent manner.
abstract: We studied whether acetaldehyde, which is produced by alcohol consumption, impacts ryanodine receptor (RyR) activity and muscle force. Exposure to approximately 50-200 microM 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 microM 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 microM acetaldehyde, respectively. Fluorescence monitoring with fluo 3 demonstrated that 200-400 microM acetaldehyde induced Ca(2+) release from the sarcoplasmic reticulum (SR) in frog muscles. Acetaldehyde at 1 mM inhibited twitch tension by approximately 12%, with an increased relaxation time after a small, transient twitch potentiation. These results suggest that moderate concentrations of acetaldehyde can elicit Ca(2+) 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 microM) are unlikely to mediate alcohol-induced acute muscle dysfunction.
authors.affiliation: Dept. of Regulatory Cell Physiology, Nagoya City Univ. Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. tooba@med.nagoya-cu.ac.jp
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Oba
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Maeno
mesh_terms: D000079:Acetaldehyde / Q000008:administration & dosage*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects*; D011817:Rabbits; D011892:Rana catesbeiana; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D000079:Acetaldehyde; D002118:Calcium