Effect of magnesium on calcium-induced depolarisation of mitochondrial transmembrane potential.
An effect of magnesium on calcium-induced depolarisation of mitochondrial transmembrane potential (DeltaPsi(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 DeltaPsi(m). Irreversible collapse of DeltaPsi(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 DeltaPsi(m) in the absence of Mg(2+). Involvement of mPTP in the process of Ca(2+)-induced collapse of DeltaPsi(m) was further supported by protective effect of both CsA and ADP. Reversible collapse of DeltaPsi(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 DeltaPsi(m) mainly through discrimination between low- and high-conductance modes of mPTP. Minor effect of Mg(2+) on Ca(2+)-induced depolarisation of DeltaPsi(m) was observed at the level of stimulation of DeltaPsi(m) generation and inhibition of mitochondrial Ca(2+) uptake.
Racay
Peter
P
Institute of Biochemistry, Jessenius Faculty of Medicine, Comenius University, Martin, Slovak Republic. racay@jfmed.uniba.sk
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012430:Ruthenium Red / Q000494:pharmacology
D012430:Ruthenium Red; D000001:Calcimycin; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D016572:Cyclosporine; D008274:Magnesium; D002118:Calcium