30 Mitochondria are the major effectors of cardioprotection by procedures that open the 31 mitochondrial ATP-sensitive potassium channel (mitoKATP), including ischemic and 32 pharmacological preconditioning. MitoKATP opening leads to increased reactive oxygen 33 species (ROS), which then activate a mitoKATP-associated PKCε, which phosphorylates 34 mitoKATP and leaves it in a persistent open sta...

OBJECTIVE Infarct size (IS) reduction by ischemic preconditioning (IPC) has been assessed in the heart in which coronary stenosis (CS)-induced chronic ischemia was not present. The aim of this study is to assess whether and how IS reduction by IPC is modified in the heart in which CS has occurred, and how further therapeutics, if any, modify it. METHODS We assessed the IS produced by a 30-min...

Background Our laboratory has shown that phosphodiesterase-5 (PDE-5) inhibitors including sildenafil, vardenafil and tadalafil induce powerful protection against myocardial ischemia-reperfusion injury. We have shown that sildenafil protects through activation PKC, expression of eNOS/ iNOS, protein kinase G (PKG) and opening of mitochondrial KATP (mitoKATP) channels [1]. Hydrogen sulfide (H2S) i...

Twenty years after the discovery of sarcolemmal ATP-sensitive K channels and 12 years after the discovery of mitochondrial KATP (mitoKATP) channels, progress has been remarkable, but many questions remain. In the case of the former, detailed structural information is available, and it is well accepted that the channel couples bioenergetics to cellular electrical excitability; however, in the he...

Superoxide (O2(·-)) production by the NADPH oxidases is implicated in the pathogenesis of many cardiovascular diseases, including hypertension. We have previously shown that activation of NADPH oxidases increases mitochondrial O2(·-) which is inhibited by the ATP-sensitive K(+) channel (mitoKATP) inhibitor 5-hydroxydecanoic acid and that scavenging of mitochondrial or cytoplasmic O2(·-) inhibit...

Background. ATP-sensitive K+ channels of the plasma membrane in smooth muscles uterus are one most significant ion that regulate excitability this tissue both non-pregnant state and during pregnancy. MitoKATР-channels ensure regulation bioenergetic mitochondria (the intensity mitochondrial respiration potential inner membrane). Thus far, there is no information on participation types these mech...

Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) f...

In the present study, we studied the mechanism of mitochondrial ATP-sensitive potassium (mitoKATP) channels regulating hypoxia-inducible factor (HIF)-1α/microRNA (miR)-210/mitochondrial iron-sulfur protein integrin (ISCU) signaling axis and forming a positive feedback loop in chronic hypoxia-induced pulmonary arterial hypertension (PAH) by using in vivo animal model. Two hundred healthy adult S...

Opening of mitochondrial ATP-sensitive (mitoKATP) channel with diazoxide induces an early phase (EP) of cardioprotection. It is unknown whether diazoxide also induces a delayed phase (DP) of cardioprotection. Because nitric oxide (NO) modulates ATP sensitivity of the KATP channel, we hypothesized that NO may play a role in diazoxide-induced cardioprotection. Diazoxide (1 mg/kg) was administered...