Ba 2+ ions inhibit the release of Ca 2+ ions from rat liver mitochondria

Abstract

The release of Ca 2+ from respiring rat liver mitochondria following the addition of either ruthenium red or an uncoupler was measured by a Ca 2+-selective electrode or by 45Ca 2+ technique. Ba 2+ ions are asymmetric inhibitors of both Ca 2+ release processes. Ba 2+ ions in a concentration of 75 μM inhibited the ruthenium red and the uncoupler induced Ca 2+ release by 80% and 50%, respectively. For the inhibition, it was necessary that Ba 2+ ions entered the matrix space: Ba 2+ ions did not cause any inhibition of Ca 2+ release if addition of either ruthenium red or the uncoupler preceded that of Ba 2+. The time required for the development of the inhibition of the Ca 2+ release and the time course of 140Ba 2+ uptake ran in parallel. Ba 2+ accumulation is mediated through the Ca 2+ uniporter as 140Ba 2+ uptake was competitively inhibited by extramitochondrial Ca 2+ and prevented by ruthenium red. Due to the inhibition of the ruthenium red insensitive Ca 2+ release, Ba 2+ shifted the steady-state extramitochondrial Ca 2+ concentration to a lower value. Ba 2+ is potentially a useful tool to study mitochondrial Ca 2+ transport.