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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/H121    most recent 00520.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Oba, T. Articles by Murayama, T. Search for Related Content PubMed PubMed Citation Articles by Oba, T. Articles by Murayama, T.

Cellular redox state protects acetaldehyde-induced alteration in cardiomyocyte function by modifying Ca²⁺ release from sarcoplasmic reticulum

Departments of ¹Cell Physiology, ²Forensic Medicine, and ³Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences, Nagoya; and ⁴Department of Pharmacology, Juntendo University School of Medicine, Tokyo, Japan

Submitted 1 May 2007 ; accepted in final form 30 October 2007

Recent studies indicate that low concentrations of acetaldehyde may function as the primary factor in alcoholic cardiomyopathy by disrupting Ca²⁺ handling or disturbing cardiac excitation-contraction coupling. By producing reactive oxygen species, acetaldehyde shifts the intracellular redox potential from a reduced state to an oxidized state. We examined whether the redox state modulates acetaldehyde-induced Ca²⁺ handling by measuring Ca²⁺ transient using a confocal imaging system and single ryanodine receptor type 2 (RyR2) channel activity using the planar lipid bilayer method. Ca²⁺ transient was recorded in isolated rat ventricular myocytes with incorporated fluo 3. Intracellular reduced glutathione level was estimated using the monochlorobimane fluorometric method. Acetaldehyde at 1 and 10 µM increased Ca²⁺ transient amplitude and its relative area in intact myocytes, but acetaldehyde at 100 µM decreased Ca²⁺ transient area significantly. Acetaldehyde showed a minor effect on Ca²⁺ transient in myocytes in which intracellular reduced glutathione content had been decreased against challenge of diethylmaleate to a level comparable to that induced by exposure to 50 µM acetaldehyde. Channel activity of the RyR2 with slightly reduced cytoplasmic redox potential from near resting state (–213 mV) or without redox fixation was augmented by all concentrations of acetaldehyde (1–100 µM) used here. However, acetaldehyde failed to activate the RyR2 channel, when the cytoplasmic redox potential was kept with a reduced (–230 mV) or markedly oxidized (–180 mV) state. This result was similar to effects of acetaldehyde on Ca²⁺ transient in diethylmaleate-treated myocytes, probably being in oxidized redox potential. The present results suggest that acetaldehyde acts as an RyR2 activator to disturb cardiac muscle function, and redox potential protects the heart from acetaldehyde-induced alterations in myocytes.

Ca²⁺ transient; single ryanodine receptor type 2 channel activity; intracellular glutathione level; intracellular redox state