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

An effect of magnesium on calcium‐induced depolarisation of mitochondrial transmembrane potential (ΔΨ m ) was investigated. Depending on the presence of Mg 2+ , addition of Ca 2+ to suspension of isolated rat heart mitochondria induced either reversible depolarisation or irreversible collapse of succinate‐driven ΔΨ m . Irreversible collapse of ΔΨ m , observed in the absence of Mg 2+ , was insensitive to Ca 2+ chelation, inhibition of Ca 2+ uptake and increased efflux of Ca 2+ from mitochondrial matrix. Based on these data, opening of mPTP in a high‐conductance mode is considered to be a major cause of the Ca 2+ ‐induced irreversible collapse of ΔΨ m in the absence of Mg 2+ . Involvement of mPTP in the process of Ca 2+ ‐induced collapse of ΔΨ m was further supported by protective effect of both CsA and ADP. Reversible collapse of ΔΨ m , observed in the presence of Mg 2+ , was sensitive to EGTA, ADP; and inhibition of Ca 2+ uptake and increased efflux of Ca 2+ from mitochondrial matrix. This may represent selective induction of a low‐conductance permeability pathway. Presented results indicate important role of Mg 2+ in the process of Ca 2+ ‐induced depolarisation of ΔΨ m mainly through discrimination between low‐ and high‐conductance modes of mPTP. Minor effect of Mg 2+ on Ca 2+ ‐induced depolarisation of ΔΨ m was observed at the level of stimulation of ΔΨ m generation and inhibition of mitochondrial Ca 2+ uptake.