New fluorine-containing openers of ATP-sensitive potassium channels flokalin and tioflokalin inhibit calcium-induced mitochondrial pore opening in rat hearts [

Exercise restores endogenous H2S synthesis and mitochondrial function in the heart of old rats

“…Increased sensitivity of mPTP to inducers of its opening we observed at the lowered levels of endogenous production of hydrogen sulphide (H 2 S) in heart of old rats 5 . Simultaneously, mechanisms to prevent the mPTP opening may be based on reducing the factors inducing its formation or reducing sensitivity to elevated calcium levels, including endogenous pore‐opening inhibitors, antioxidants, ATP‐sensitive potassium channels (K ATP channels), the regulators of an influx of calcium ions in the mitochondria, some gaseous transmitters and other endogenous factors 6–8 . In particular, we have shown the inhibition of mPTP formation in experiments on suspensions mitochondria and the associated reduction in the processes of necrosis and apoptosis in anoxia‐reoxygenation of neonatal cardiomyocytes by pharmacological activators of K ATP channels flocalin and tioflocalin 6,9 .…”

“…[6][7][8] In particular, we have shown the inhibition of mPTP formation in experiments on suspensions mitochondria and the associated reduction in the processes of necrosis and apoptosis in anoxia-reoxygenation of neonatal cardiomyocytes by pharmacological activators of K ATP channels flocalin and tioflocalin. 6,9 In a series of experiments involving cofactor H 2 S-synthesizing enzymes pyridoxal-5-phosphate and hydrogen sulfide donor NaHS at reduced levels of endogenous H 2 S production in the heart of old rats, we observed increased hydrogen sulfide levels, reduced oxidative stress, and better recovery of function of the ischemic heart during reperfusion that proves the important role of this gaseous transmitter in the regulation of mitochondrial function. 5,10 H 2 S is an important endogenously synthesized signaling molecule synthesized by three enzymes, two of which have a pronounced expression in the cardiovascular system, namely 3-mercaptopyruvate sulfurtransferase (3-MST), which is localized mainly in mitochondria, where it functions together with cysteine aminotransferase (CAT) and cystathionine-γlyase (CSE) in the cytosol of cells.…”

“…Simultaneously, mechanisms to prevent the mPTP opening may be based on reducing the factors inducing its formation or reducing sensitivity to elevated calcium levels, including endogenous pore‐opening inhibitors, antioxidants, ATP‐sensitive potassium channels (K ATP channels), the regulators of an influx of calcium ions in the mitochondria, some gaseous transmitters and other endogenous factors 6–8 . In particular, we have shown the inhibition of mPTP formation in experiments on suspensions mitochondria and the associated reduction in the processes of necrosis and apoptosis in anoxia‐reoxygenation of neonatal cardiomyocytes by pharmacological activators of K ATP channels flocalin and tioflocalin 6,9 . In a series of experiments involving cofactor H 2 S‐synthesizing enzymes pyridoxal‐5‐phosphate and hydrogen sulfide donor NaHS at reduced levels of endogenous H 2 S production in the heart of old rats, we observed increased hydrogen sulfide levels, reduced oxidative stress, and better recovery of function of the ischemic heart during reperfusion that proves the important role of this gaseous transmitter in the regulation of mitochondrial function 5,10 .…”

Upregulation of ATP-Sensitive Potassium Channels as the Potential Mechanism of Cardioprotection and Vasorelaxation Under the Action of Pyridoxal-5-Phosphate in Old Rats

“…This prevents excessive accumulation of calcium in the mitochondria, enhances their resistance to this ion, and prevents mPTP opening. [45][46][47] Signaling pathway: mitoK ATP channels opening/increasing ROS/activation of protein kinase Cϵ 2 also prevents mPTP opening and apoptosis. 48 The entry of potassium ions into the mitochondrion at the opening of mitoK ATP channels is accompanied by the entry of inorganic phosphate and water (which leads to moderate osmotic swelling of the mitochondrial matrix), changes in respiration and phosphorylation processes, and alkalosis of the mitochondrial matrix.…”

Nephroprotective properties of ATP-sensitive potassium channels agonist flocalin

“…Overload of the mitochondrial matrix with calcium ions leads to opening of MP -a principal regulator of their function and swelling of organelles. In experiments with calcium-induced swelling of mitochondria it was shown that activation of calcium-selective permeability of inner mitochondrial membrane leads to dosedependent inhibition of MP opening in heart, indicating the anti-ischemic, anti-apoptotic effects of flocalin as well as its efficacy against mitochondrial dysfunction [38].…”