We tested whether opening of mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channels depolarizes mitochondrial membrane potential (DeltaPsi(m)) and thereby prevents the mitochondrial Ca(2+) overload. With the use of a Nipkow disk confocal system, the mitochondrial Ca(2+) concentration ([Ca(2+)](m)) and DeltaPsi(m) in rat ventricular myocytes were measured by loading cells with Rhod-2 and JC-1, r...

BACKGROUND Our recent study has demonstrated that inhibition of calpain by transgenic overexpression of calpastatin reduces myocardial proinflammatory response and dysfunction in endotoxemia. However, the underlying mechanisms remain to be determined. In this study, we used cardiomyocyte-specific capn4 knockout mice to investigate whether and how calpain disrupts ATP synthase and induces mitoch...

Myocardial ATP-gated potassium channels (K-ATPs) are critical in the intracellular signaling cascade resulting in ischemic preconditioning (IP). Mitochondrial K-ATP channels seem to be responsible for IP, whereas the functions of K-ATP channels in the sarcolemmal membrane are less well understood. The proarrhythmic potential of specific versus nonspecific opening of K-ATP channels has not been ...

The toxicity of tributyltin chloride (TBT) involves Ca(2+) overload, cytoskeletal damage, and mitochondrial failure leading to cell death by apoptosis or necrosis. Here, we examined whether the intracellular ATP level modulates the mode of cell death after exposure to TBT. When Jurkat cells were energized by the mitochondrial substrate, pyruvate, low concentrations of TBT (1-2 microM) triggered...

objective: several recent studies have shown that mitochondrial dna mutations lead to major disabilities and premature death in carriers. more than 150 mutations in human mitochondrial dna (mtdna) genes have been associated with a wide spectrum of disorders. varicocele, one of the causes of infertility in men wherein abnormal inflexion and distension of veins of the pampiniform plexus is observ...

Pancreatic β-cells sense glucose, promoting insulin secretion. Glucose sensing requires the sequential stimulation of glycolysis, mitochondrial metabolism and Ca2+ entry. To elucidate how mitochondrial activation in β-cells contributes to insulin secretion, we compared the effects of glucose and the mitochondrial substrate methylsuccinate in the INS-1E insulin-secreting cell line at the respect...

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...

The mitochondrial ATP-sensitive potassium channel (mK(ATP)) is important in cardioprotection, although the channel remains molecularly undefined. Several studies have demonstrated that mitochondrial complex II inhibitors activate the mK(ATP), suggesting a potential role for complex II in channel composition or regulation. However, these inhibitors activate mK(ATP) at concentrations which do not...

We tested whether close coupling exists between mitochondria and sarcolemma by monitoring whole cell ATP-sensitive K(+) (K(ATP)) current (I(K,ATP)) as an index of subsarcolemmal energy state during mitochondrial perturbation. In rabbit ventricular myocytes, either pinacidil or the mitochondrial uncoupler dinitrophenol (DNP), which rapidly switches mitochondria from net ATP synthesis to net ATP ...

Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are ...