Journal archive > 2004 > #1 January-February


Induction of the mitochondrial pore opening as affected by Ca2+ in the rat myocardium

O. V. AkopovaV. F. Sagach

The mitochondrial role opening (MPT) induced by Ca2+ has been studied in isolated rat heart mitochondria. MPT was characterized as cyclosporine A-nhibited swelling accompanied by the loss of membrane potential (??m) and Ca2+ efflux after the Ca2+-loading which was followed spectrophotometrically after the Ca2+-arsenaso-III complex formation.

It has been shown that in suspension of isolated mitochondria MPT was activated by low (with maximum at about 20 mM Ca2+) and high concentrations of Ca2+ (the concentration curve shows a saturation at about 1.0–1.5 mM). In all the cases an access of Ca2+ ions to the matrix space of the mitochondria was necessary for MPT induction.

MPT activated by low concentrations of Ca2+ was accompanied by slow decrease of ??m and slow release of Ca2+, enhanced by ruthenium red (RR), and was independent of the substrate used (glutamate or succinate). It had not been observed if the respiratory chain was inhibited, even if the Ca2+ access to the inner mitochondrial membrane was provided by Ca2+-ionophore A23187.

At high Ca2+ concentrations rapid Ca2+-uptake and release via Ca2+-uniporter (inhibited by ruthenium red) followed by extensive swelling (pore formation) have been observed. It had been supposed that rapid MPT at high concentrations of Ca2+ was the result of Ca2+ entrance to the mitochondrial matrix and depolarisation of the mitochondrial membrane.

The data obtained show two different mechanisms of Ca2+-induced MPT. The one is sensitive to the redox-state of the electron transport chain and is abolished if the respiration is inhibited. The other is independent of mitochondrial respiration and needs only Ca2+ access to the inner mitochondrial membrane and Ca2+ binding to some specific sites leading to MPT opening.

Recieved: 2003-10-03

Published at the site: 2004-02-02

The original article in Russian is available for download in PDF format.