Release of Ca2+ from mitochondria after mitochondrial membrane depolarisation
With the aid of specific inhibitors of Са2+-uniporter (ruthenium red) and mitochondrial permeability transition pore, PTP (cyclosporine A) it is shown that PTP opening takes place after loading the rat liver mitochondria with calcium and depolarisation of mitochondrial membrane with protonophore (carbonyl cyanide m-chlorophenyl hydrazone, CCCP), and the pore opening accounts for accelerated efflux of calcium from mitochondrial matrix as well as availability of “rapid” component of two-exponential kinetic curve of Са2+-efflux. An analysis of kinetic data of Са2+ transport after membrane depolarisation also confirms our earlier observations that time frame of the pore open state is restricted, and membrane integrity is restored before all the calcium load is delivered into incubation medium.
The absence of additivity between the shares of Са2+-uniporter and PTP in Са2+-transport is observed, and conclusion is made that partial share of PTP in calcium transport is not a constant, but a variable constituent which is diminished to zero as soon as the Са2+-uniporter activity reaches its maximum after the abolition of membrane potential with CCCP.
Based on some observations, it is supposed also that PTP inactivation takes place during calcium translocation across the mitochondrial membrane, which could account for limited release of Са2+ from mitochondrial matrix through the pore itself as well as relatively narrow limits of the pore open state in comparison with time scale of complete cation release from depolarised mitochondria.
Published at the site: 2005-10-10
The original article in Russian is available for download in PDF format.
© The Ukrainian Biochemical Journal