Potassium (K+) channels in the inner mitochondrial membrane influence cell function and survival. Increasing evidence indicates that multiple signaling pathways and pharmacological actions converge on mitochondrial ATP-sensitive K+ (mitoKATP) channels and PKC to confer cytoprotection against necrotic and apoptotic cell injury. However, the molecular structure of mitoKATP channels remains unreso...

Activation of the mitochondrial ATP-sensitive K+ channel (mitoKATP) and its regulation by PKC are critical events in preconditioning induced by ischemia or pharmaceutical agents in animals and humans. The properties of the human cardiac mitoKATP channel are unknown. Furthermore, there is no evidence that cytosolic PKC can directly regulate the mitoKATP channel located in the inner mitochondrial...

Mitochondria are key mediators of the cardioprotective signal and the mitochondrial ATP-sensitive K channel (mitoKATP) plays a crucial role in originating and transmitting that signal. Recently, protein kinase C (PKC ) has been identified as a component of the mitoKATP signaling cascade. We hypothesized that PKC and mitoKATP interact directly to form functional signaling modules in the inner mi...

Pharmacological openers of mitochondrial ATP-dependent K+ (mitoKATP) channels mimic ischemic preconditioning, and such cardioprotection can be prevented by mitoKATP channel blockers. It is also known that protein kinase C (PKC) plays a key role in the induction and maintenance of preconditioning. To look for possible mechanistic links between these 2 sets of observations, we measured mitochondr...

A variety of direct and indirect techniques have revealed the existence of ATP-sensitive potassium (KATP) channels in the inner membranes of mitochondria. The molecular identity of these mitochondrial KATP (mitoKATP) channels remains unclear. We used a pharmacological approach to distinguish mitoKATP channels from classical, molecularly defined cardiac sarcolemmal KATP (surfaceKATP) channels en...

This study aimed to investigate the effects of mitochondrial ATP-sensitive potassium (MitoKATP) channel opening on the translocation of protein kinase C epsilon (PKCε). In addition, we aimed to determine the relationship between PKCε translocation and the production of reactive oxygen species (ROS). PKCε protein expression in cultured adult rat ventricular myocytes was investigated by immunoflu...

Mitochondrial ATP-sensitive potassium (mitoKATP) channels play a key role in ischemic preconditioning of the heart. However, the mechanism of cardioprotection remains controversial. We measured rhod-2 fluorescence in adult rabbit ventricular cardiomyocytes as an index of mitochondrial matrix Ca concentration ([Ca ]m), using time-lapse confocal microscopy. To simulate ischemia and reperfusion (I...

The mitochondrial ATP-sensitive K(+) (mitoKATP) channel plays a significant role in mitochondrial physiology and protects against ischemic reperfusion injury in mammals. Although fish frequently face oxygen fluctuations in their environment, the role of the mitoKATP channel in regulating the responses to oxygen stress is rarely investigated in this class of animals. To elucidate whether and how...

Mitochondria are the major effectors of cardioprotection by procedures that open the mitochondrial ATP-sensitive potassium channel (mitoKATP), including ischemic and pharmacological preconditioning. MitoKATP opening leads to increased reactive oxygen species (ROS), which then activate a mitoKATP-associated PKCε, which phosphorylates mitoKATP and leaves it in a persistent open state (Costa AD, G...

Ischemic and pharmacological preconditioning can be triggered by an intracellular signaling pathway in which Gi-coupled surface receptors activate a cascade including phosphatidylinositol 3-kinase, endothelial nitric oxide synthase, guanylyl cyclase, and protein kinase G (PKG). Activated PKG opens mitochondrial KATP channels (mitoKATP) which increase production of reactive oxygen species. Steps...