FIGURE 4.

How increased K⁺ conductance may improve mitochondrial calcium retention and sensitivity to permeability transition. Schematic illustrations are shown of some proposed physiological effects caused by increased K⁺ conductance under conditions where mitochondria buffer an increased cytoplasmic calcium load. Increased K⁺ conductance by K⁺ channel activation or by the K⁺-carrier valinomycin may enhance matrix alkalization via increased H⁺ extrusion by the electron transport chain (ETC). The uptake of phosphate (P_i) and the equilibrium between differently protonated phosphate groups each depends on pH. An alkaline pH enhances the availability of PO₄³⁻, enabling formation of calcium phosphate complexes (e.g. Ca₃(PO₄)₂) from free Ca²⁺. Enhanced matrix volume due to the osmotic effect of K⁺ may also lead to increased availability of P_i and enhanced calcium complex formation. The maintenance of low [Ca²⁺] in the mitochondrial matrix reduces the sensitivity of mPT and may, therefore, increase CRC. Increased K⁺ conductance has further been suggested to elevate mitochondrial ROS production, which activates PKCϵ and, through its claimed association with the mPT pore complex, induces resistance to mPT (22, 44, 53).