Abstract
Acetaldehyde (AcA), an oxidized product of alcohol, may contribute to alcohol-induced cardiac muscle dysfunction. Recently, we have demonstrated that even at 1-3 μM, AcA activates the ryanodine receptor type 2 (RyR2) channel and promotes Ca2+ release from the cardiac muscle SR (Oba et al., JJP 55:S90, 2005). AcA produces ROS and oxidizes GSH to GSSG to lead to oxidative stress in tissues. We studied whether cytoplasmic redox potential (RP) affects AcA-induced activation of the RyR2 channel and mediates cardiac dysfunction. In experiments under RP control using glutathione buffers, fixation of cytoplasmic (cis) RP at the oxidative state activated the channel incorporated into bilayers, whereas definition of luminal (trans) potential did not. Exposure of the RyR2 to AcA without defining RP stimulated markedly the channel in a dose-dependent manner (1-100 μM). When RP in cis/trans sides of the channel was fixed at -220/-180 mV, AcA at concentrations less than 3 μM caused no longer the channel activation, but higher concentrations increased 2 fold the open probability. In condition under cis/trans potential at -250/-180mV, AcA failed to activate the RyR2 channel. These results indicate that the activation of RyR2 channels by AcA exposure is elicited even at reductive states and suggest that cytoplasmic RP may have a protective effect against pathophysiological changes by AcA in cardiac myocytes. [J Physiol Sci. 2006;56 Suppl:S127]
