Temperature dependence of the mitochondrial inner membrane anion channel - The relationship between temperature and inhibition by protons

In this paper, we investigate the temperature and pH dependence of the mitochondrial inner membrane an ion channel (IMAC) that is believed to be involved in mitochondrial volume homeostasis, At pH 7.4, the flux oil malonate is highly temperature-dependent with rates; increasing from 1 nmol/min . mg at 5 degrees C to 1900 nmol/min . mg at 45 degrees C, The Arrhenius plot is nonlinear with the activation energy increasing from 21 kJ/mol (Q(10) = 1.3) to 193 kJ/mol (Q(10) = 13) as the temperature is decreased. This temperature dependence is unusual and not seen with solutes that are transported through the bilayer such as NH4OAc, malonamide, and KSCN (plus valinomycin) or even for cytochrome c oxidase-depend ent uptake of potassium (plus valinomycin), The temperature dependence of IMAC is closely related to the inhibition of IMAC by protons, Thus, we find that the pIC(50) for protons decreases from 9.3 (Hill coefficient = 1.0) at 5 degrees C to 7.1 (Hill coefficient = 2.5) at 45 degrees C, This behavior is explained on the basis of a new kinetic model for IMAC in which the net open probability is not only modulated by the binding of three protons but also by temperature via effects on the open probability of the unprotonated channel and the pK of one of the inhibitory protonation sites.