Fig. 2. Cellular preservation during ischemia-reperfusion injury may be mediated by the opening of mitochondrial adenosine triphosphate-sensitive potassium (mito KATP) channels concomitant with modest modulation of mitochondrial function. Depolarization of the inner mitochondrial membrane and matrix swelling occur as a consequence of mito KATPchannel opening (1 ). Membrane depolarization due to a shift in the ionic balance prevents Ca2+overload (2 ). Initial disruption of the electron transport chain may generate signaling amounts of reactive oxygen species (ROS; 3 ). Volume regulatory mechanisms (4 ) dissipate the proton gradient and uncouple adenosine triphosphate (ATP) synthesis (5 ) that ultimately maximizes oxidative phosphorylation and reduces oxidative stress. Mito KATPchannel opening can also reduce membrane permeability and prevent apoptosis and/or necrosis by maintaining nucleotide content, preserving high-energy phosphate transfer, and reducing cytochrome c release. ADP = adenosine diphosphate.