%0 Journal Article %A Strutynska, Nataliya A. %A Semenykhina, Olena M. %A Chorna, Snizhana V. %A Vavilova, Galyna L. %A Sagach, Vadim F. %D 2012 %I Begell House %K hydrogen sulfide, L-cysteine, mitohondrial permeability transition pore, heart, aging, rats %N 2 %P 135-147 %R 10.1615/IntJPhysPathophys.v3.i2.40 %T Hydrogen Sulfide Inhibits Calcium-Induced Mitohondrial Permeability Transition Pore Opening in the Heart of Adult and Old Rats %U https://www.dl.begellhouse.com/journals/6ec4ba27650016b1,551b155962667b02,040fa13c0fea18bf.html %V 3 %X Effects of NaHS, a hydrogen sulfide donor, and L-cysteine, a substrate of its biosynthesis, on the sensitivity of the mitohondrial permeability transition pore (rnPTP) to its natural inductor Ca2+ were investigated on mitochondria isolated from the heart tissues of adult and old rats in experiments in vivo and in vitro. It has been shown that NaHS at concentrations in the range between 10−12 and 10−8 mol / l induced moderate mitochondrial swelling of the rat heart in calcium-free medium. At concentration of 10−10 mol / L, NaHS caused mitochondrial swelling, and changes in its maximum size (Δ) accounted for 11% and 15% in adult and old rats, respectively. An inhibitor of mitochondrial ATP-dependent potassium channels (KATP channels) 5-hydroxydecanoate (10−4 mol / l) reduced the mitochondrial swelling in the presence of NaHS (10−10 mol / l), which may indicate a contribution of these channels to calcium-independent membrane conductance in the heart organelles. Hydrogen sulfide donor in physio-logical concentrations of 10−6, 10−5 and 5·10−5mol / l depressed calcium-induced mPTP opening, indicating its protective effect on pore formation that comprised 31%, 76% and 77%, respectively in the heart of adult rats. However, in old animals this effect was observed only at NaHS concentrations of 10−5 mol / l. Thus, hydrogen sulfide donor within the studied concentrations resulted in ambiguous effects on mPTP opening: low concentrations (10−12 − 10−8 mol / l) increased mitochondrial swelling of the organelles, but its physiological concentrations (10−6 −5·10−5 mol / l) carried protective effect on calcium-induced mitochondrial swelling in rat hearts. Preincubation of isolated mitochondria with 5-hydroxydecanoate (10−4 mol / l) reduced the protective effect of NaHS (10−5 mol / l) relative to calcium-induced mPTP opening, indicating the possible involvement of mitochondrial KATP channels in hydrogen sulfide-dependent inhibition of pore formation in the heart. In experiments in vivo with a single intraperitoneal administration of either NaHS (10−4 mol / kg) or L-cysteine (10−3 mol / kg), a decrease in mPTP sensitivity to Ca2+ inductor in the heart of adult and old rats has been shown. L-cysteine turned out to be more effective to prevent calcium-induced mPTP opening compared with NaHS: a tenfold increase in Ca2+ concentration was observed, resulting in mitochondria swelling in the heart. In in vivo experiments, a specific inhibitor of cystathionine-γ-lyase propargylglycine (10−4 mol / kg) which is involved in the biosynthesis of hydrogen sulfide, induced a significant increase in mPTP sensitivity to the Ca2+ inductor due to two orders of magnitude decrease in its threshold concentration, which, in turn, causes swelling of the organelles. Therefore, endogenous hydrogen sulfide has been shown to be envolved in the regulation of pore formation in the heart. Thus, the data obtained indicate the participation of hydrogen sulfide in the modulation of the changes in the permeability of mitochondrial membranes, which may be important regulatory factor in the development of cardiovascular diseases. %8 2012-06-09