Effect of magnesium on calcium-induced depolarisation of mitochondrial transmembrane potential

An effect of magnesium on calcium-induced depolarisation of mitochondrial transmembrane potential (ΔΨm) was investigated. Depending on the presence of Mg2+, addition of Ca2+ to suspension of isolated rat heart mitochondria induced either reversible depolarisation or irreversible collapse of succinate-driven ΔΨm. Irreversible collapse of ΔΨm, observed in the absence of Mg2+, was insensitive to Ca2+ chelation, inhibition of Ca2+ uptake and increased efflux of Ca2+ from mitochondrial matrix. Based on these data, opening of mPTP in a high-conductance mode is considered to be a major cause of the Ca2+-induced irreversible collapse of ΔΨm in the absence of Mg2+. Involvement of mPTP in the process of Ca2+-induced collapse of ΔΨm was further supported by protective effect of both CsA and ADP. Reversible collapse of ΔΨm, observed in the presence of Mg2+, was sensitive to EGTA, ADP; and inhibition of Ca2+ uptake and increased efflux of Ca2+ from mitochondrial matrix. This may represent selective induction of a low-conductance permeability pathway. Presented results indicate important role of Mg2+ in the process of Ca2+-induced depolarisation of ΔΨm mainly through discrimination between low- and high-conductance modes of mPTP. Minor effect of Mg2+ on Ca2+-induced depolarisation of ΔΨm was observed at the level of stimulation of ΔΨm generation and inhibition of mitochondrial Ca2+ uptake.