Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential

  title={Mitochondrial KATP channel activation reduces anoxic injury by restoring mitochondrial membrane potential},
  author={Meifeng Xu and Yigang Wang and Ahmar Ayub and Muhammad Ashraf},
  journal={American Journal of Physiology-heart and Circulatory Physiology},
Mitochondrial membrane potential (ΔΨm) is severely compromised in the myocardium after ischemia-reperfusion and triggers apoptotic events leading to cell demise. This study tests the hypothesis tha... 

Figures from this paper

Role of Mitochondrial Membrane Potential in Cardiac Protection against Ischemia

It is concluded that activation of mitoKATP channel with diazoxide prevented disruption of ΔΨm resulting in protection against A-R induced injury.

Evidence for Mitochondrial K+ Channels and Their Role in Cardioprotection

This review updates recent progress in understanding the physiological role of mitoKATP and highlights outstanding questions and controversies, with the intent of stimulating additional investigation on this topic.

Melatonin protection against lethal myocyte injury induced by doxorubicin as reflected by effects on mitochondrial membrane potential.

The data support the hypothesis that DOX induces damage to mitochondria through radicals, and this is reflected in depolarization of Delta(psi)(m), which was prevented by melatonin.

Is Reduced Cell Swelling a Plausible End-Effector of Ischemic Preconditioning Protection?

Evidence relevant to the novel hypothesis that reduced cellular swelling may be an end-effector of preconditioning protection is briefly reviewed below.

Controlling the Mitochondrial Protonmotive Force with Light to Impact Cellular Stress Resistance

The novel optogenetic approach demonstrated that a decreased PMF is both necessary and sufficient for hypoxia-stimulated stress resistance and is a powerful tool to modulate metabolic and cell signaling outcomes.

Cardioprotection by Mitochondrial KATP Channel in Both Early and Late Preconditioning

Data suggest that PKC activation is required for the opening of mitoKATP channels in the protection against ischemia and this effect is linked with isoform specific translocation of δ to mitochondria.

TASK-1 regulates mitochondrial function under hypoxia.




Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis.

Protection by inhibition of MPT by CsA and CPC suggests that MPT plays an important role in reoxygenation/reperfusion injury and suggests that preconditioning inhibits MPt by inhibiting Ca(2+) accumulation by mitochondria.

Mitochondrial electron transport can become a significant source of oxidative injury in cardiomyocytes.

It is demonstrated that mitochondrial ETC carriers can cause significant oxidant injury, greatest when fully redox-reduced and exposed to oxygen, conditions known to occur in the transition from ischemia to reperfusion.

Opening of potassium channels protects mitochondrial function from calcium overload.

The myocardial protective effects resulting from activating K(ATP) channels either pharmacologically or by IPC may be the result of protecting mito from Ca(2+) overload.

Mitochondrial Dysfunction in the Pathogenesis of Necrotic and Apoptotic Cell Death

Cyclosporin A blocks this mitochondrial permeability transition (MPT) and prevents necrotic cell death from oxidative stress, Ca2+ ionophore toxicity, eye-related drug toxicity, pH-dependent ischemia/reperfusion injury, and other models of cell injury.

Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?

The results demonstrate that diazoxide targets mitochondrial but not sarcolemmal KATP channels and imply that mitochondrial KatP channels may mediate the protection from KATp channel openers.

Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts.

Both NADH-generating reactions and the ATP synthase-catalyzed reaction are important in causing the increase in respiration that accompanies increased work, which indicates that the myocardium responds to alterations in cardiac work by changing its rate of O2 consumption.

Activation of mitochondrial ATP-sensitive K(+) channel for cardiac protection against ischemic injury is dependent on protein kinase C activity.

The data suggest that activation and translocation of PKC to mitochondria appear to be important for the protection mediated by mitoK(ATP) channel.

The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis

In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process.

On the Voltage Dependence of the Mitochondrial Permeability Transition Pore

It is shown that although reactive oxygen species can contribute to the permeability transition, pore opening by FCCP can still be observed under strict anaerobiosis after ATP-dependent Ca2+accumulation and that the permeable transition can be induced by the addition of valinomycin to respiring mitochondria treated with nigericin in low potassium medium.