Glutathione Upregulates the Expression of K_ATP Channels and Vasorelaxation Responses and Inhibits mPTP Opening and Oxidative Stress in the Heart Mitochondria of Old Rats

Figure 3

Effects of glutathione, modulators of glutathione synthesis, and K_ATP channel activity on the Ca²⁺-induced mPTP opening in heart of adult (6 months) and old (24 months) rats. (a) Effect of K_ATP channel modulators flocalin (10 μmol/L) and 5-HD (100 μmol/L) on Ca²⁺-induced swelling of heart mitochondria of adult rats (typical native curves). (b) The action of K_ATP channel modulators flocalin (100 μmol/L) and 5-HD (100 μmol/L) on Ca²⁺-induced swelling of heart mitochondria of old rats (typical native curves). (c) Comparison of the amplitude of control (without calcium) and calcium-dependent swelling of heart mitochondria of adult and old rats. (d) The sensitivity of mPTP to calcium in the heart of adult and old rats, as well as under the conditions of action of the inhibitor of glutathione synthesis BSO in the heart of adult rats. (e) Influence of glutathione and its synthesis inhibitor BSO, K_ATP channel opener flocalin, and mPTP inhibitor Cs A on the amplitude of Ca²⁺-induced swelling (Ca²⁺, 100 μmol/L) of heart mitochondria of adult and old rats. Glutathione and BSO were applied in vivo. GSH: glutathione; Cs A: classical mPTP inhibitor cyclosporin A; BSO: an inhibitor of glutathione synthesis DL-buthionine-S,R-sulfoximine; Fl: opener of K_ATP channels flocalin; 5-HD: an inhibitor of mitochondrial K_ATP channels 5-hydroxydecanoate. Data are represented as . For adult rats, ; for old rats, ; for old glutathione-treated rats, . ^& compared to control adult rats (Ca²⁺-free medium); ^# compared to control old rats (Ca²⁺-free medium); compared to Ca²⁺-induced swelling of heart mitochondria of adult rats; ^$ compared to Ca²⁺-induced swelling of heart mitochondria of old rats. The use of exogenous glutathione and its synthesis inhibitor BSO and K_ATP channel activity modulators flocalin and 5-HD in studies allowed us to draw conclusions about the regulation of pore formation with the help of glutathione, as well as about the effect of activation of K_ATP channels on inhibition of mPTP. Increased sensitivity of mPTP to its calcium inducer was shown in old animals. The mitoprotective effect of exogenous glutathione in its reduced form was manifested by partial inhibition of Ca²⁺-induced mPTP opening.

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