Mersalyl prevents the Tl + -induced permeability transition pore opening in the inner membrane of Ca 2+ -loaded rat liver mitochondria

摘要

Abstract It was earlier shown that the calcium load of rat liver mitochondria in medium containing TlNO 3 and KNO 3 resulted in the Tl + -induced mitochondrial permeability transition pore (MPTP) opening in the inner membrane. This opening was accompanied by an increase in swelling and membrane potential dissipation and a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration. This respiratory decrease was markedly leveled by mersalyl (MSL), the phosphate symporter (PiC) inhibitor which poorly stimulated the calcium-induced swelling, but further increased the potential dissipation. All of these effects of Ca 2+ and MSL were visibly reduced in the presence of the MPTP inhibitors (ADP, N-ethylmaleimide, and cyclosporine A). High MSL concentrations attenuated the ability of ADP to inhibit the MPTP. Our data suggest that the PiC can participate in the Tl + -induced MPTP opening in the inner membrane of Ca 2+ -loaded rat liver mitochondria. Highlights ? Interdependent participation of ANT and PiC is proposed in Tl + -induced pore opening. ? Hydrophilic reagent mersalyl (MSL) till 5?μM inhibited opening the Tl + -induced pore. ? The inhibiting effect of MSL was enhanced in experiments with N-ethylmaleimide. ? The MSL inhibition of the pore opening was maximal in the presence of ADP and CsA. ? Ability of ADP to inhibit the pore decreased in experiments with 20?μM MSL.