It is concluded that respiratory uncoupling is not directly beneficial to rat heart mitochondrial resistance to calcium overload irrespective of whether H + or K + conductance is increased. The H 2O 2 detoxification was dependent on respiratory substrates and was dramatically decreased following calcium-induced mPT, but was unaffected by uncoupling via increased K + and H + conductance. The ability of heart mitochondria to detoxify H 2O 2 was substantially greater than the production rate. ROS generation was reduced by both K +- and H +-mediated respiratory uncoupling. However, mitochondria in hypoosmolar buffer to increase matrix volume did not display increased CRC. Mitochondria suspended in hyperosmolar buffer demonstrated a dose-dependent reduction in CRC with increasing osmolarity. Simultaneous monitoring of mitochondrial respiration and calcium retention capacity (CRC) demonstrated that the relative increase in respiration caused by valinomycin or CCCP correlated with a decrease in CRC, and that no level of respiratory uncoupling was associated with enhanced resistance to mPT. Isolated rat heart mitochondria were exposed to a wide concentration range of the protonophore CCCP or the potassium ionophore valinomycin to induce increased H + and K + conductance, respectively. The objectives of the present study were to explore how increased H + and K + fluxes influence heart mitochondrial physiology with regard to production and scavenging of reactive oxygen species (ROS), volume changes and resistance to calcium-induced mitochondrial permeability transition (mPT). Ischemic preconditioning has been proposed to involve changes in mitochondrial H + and K + fluxes, in particular through activation of uncoupling proteins and ATP-sensitive K + channels (MitoK ATP).

What is cccp mean biology