CALCIUM ION ACCUMULATION AND VOLUME CHANGES OF ISOLATED LIVER MITOCHONDRIA. CALCIUM ION-INDUCED SWELLING

Abstract

Rat liver mitochondria suspended in an iso-osmotic buffered K Cl medium containing an oxidizable substrate and phosphate accumulated added Ca2+. During this process H+ appeared in the medium and the mitochondrial suspension showed increased light-scattering. Respiration was markedly stimulated. The addition of excess of Ca2+, respiratory inhibitors or uncoupling agents caused extensive mitochondrial swelling associated with release of Ca2+, into the suspending medium. When the suspension became anaerobic extensive swelling also occurred. Only under conditions when the addition of uncoupling agents would have produced high rates of electron transport, e. g. in the presence of succinate, was the structural integrity of the mitochondrion maintained after Ca2+ accumulation. Conditions that prevented respiration-depondent Ca2+ accumulation also prevented Ca2+-induced swelling. Bovine plasma albumin was without effect, indicating that U-factor was not involved. Oligomycin together with ADP or ATP partially stabilized the mitochondria against Ca2+-induced swelling. It is suggested that a ''high-energy'' intermediate generated by coupled electron transport is required to prevent the mitochondrial swelling that results as a consequence of Ca2+ accumulation.