mKATP activity, and used this assay probe several aspects of mKATP function. The following key observations were made. (1) Time-dependent run down of mKATP activity was reversed by phosphatidylinositol-4,5bisphosphate (PIP2). (2) Dose responses of mKATP to nucleotides revealed a UDP EC50 of 20 mol/L and an ATP IC50 of 5 mol/L. (3) The antidepressant fluoxetine (Prozac) inhibited mKATP (IC50 2.4...

PURPOSE To examine the mechanisms of ischemic preconditioning (IPC) related to the opening of mitochondrial KATP (mKATP) channels in the retina. METHODS Rats were subjected to retinal ischemia after IPC, or retinas were rendered ischemic after pharmacological opening of mKATP channels. The effects of blocking mKATP channel opening, nitric oxide synthase (NOS) subtypes, or protein kinase C (PK...

Mitochondrial (m) KATP channel opening has been implicated in triggering cardiac preconditioning. Its consequence on mitochondrial respiration, however, remains unclear. We investigated the effects of two different KATP channel openers and antagonists on mitochondrial respiration under two different energetic conditions. Oxygen consumption was measured for complex I (pyruvate/malate) or complex...

BACKGROUND Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC. M...

ATP-sensitive K(+) (KATP) channels that contain K(+) inward rectifier subunits of the 6.2 isotype (Kir6.2) are important regulators of the cardiac response to ischemia-reperfusion (I/R) injury. Opening of these channels is implicated in the cardioprotective mechanism of ischemic preconditioning (IPC), but debate surrounds the contribution of surface KATP (sKATP) versus mitochondrial KATP (mKATP...

Loss of mitochondrial membrane potential (ΔΨm) is known to be closely linked to cell death by various insults. However, whether acceleration of the ΔΨm recovery process prevents cell necrosis remains unclear. Here we examined the hypothesis that facilitated recovery of ΔΨm contributes to cytoprotection afforded by activation of the mitochondrial ATP-sensitive K+ (mKATP) channel or inactivation ...

BACKGROUND Mitochondrial permeability transition pore (mPTP) opening is a terminal event leading to mitochondrial dysfunction and cell death under conditions of oxidative stress (OS). However, mPTP blockade with cyclosporine A (CsA) has shown variable efficacy in limiting post-ischemic dysfunction and arrhythmias. We hypothesized that strong feedback between energy dissipating (mPTP) and cardio...

A substantial body of evidence indicates that pharmacological activation of mitochondrial ATP-sensitive potassium channels (mKATP) in the heart is protective in conditions associated with ischemia/reperfusion injury. Several mechanisms have been postulated to be responsible for cardioprotection, including the modulation of mitochondrial respiratory function. The aim of the present study was to ...

Nitric oxide (NO) and reactive oxygen species (ROS) are double-edged swords in reperfused hearts. The effects of a NO-donor and an antioxidant compound against ischemia/reperfusion were studied. The compounds were tested separately, as a mixture and as a new hybrid molecule containing both leads. Isolated rat hearts underwent 30 min global ischemia and 2 hrs reperfusion. Compounds were infused ...

Ischemic preconditioning (IPC) has been considered to be a potential therapy to reduce ischemia-reperfusion injury (IRI) since the 1980s. Our previous study indicated that sevoflurane preconditioning (SPC) also reduced intestinal IRI in rats. However, whether the protective effect of SPC is similar to IPC and the mechanisms of SPC are unclear. Thus, we compared the efficacy of SPC and IPC again...