Inhibition of Ca²⁺ efflux from mitochondria by nupercaine and tetracaine

Abstract

IT was reported by Mela^1,2 that local anaesthetics stimulate Ca²⁺ uptake by rat liver mitochondria. This has been attributed to the protective action of these compounds on mitochondrial structure^3,4, particularly with regard to inhibition of phospholipase A (refs 5, 6). However, another possibility is that local anaesthetics affect differentially, and more directly, the uptake and efflux of Ca²⁺. Recent evidence suggests that mammalian mitochondria, in addition to the well documented route for Ca²⁺ accumulation, have a different mechanism for Ca²⁺ release^7–9. In the case of rat liver mitochondria, inhibition of Ca²⁺ uptake by the addition of ruthenium red causes a slow release of Ca²⁺ from the mitochondrial matrix^7,8 which is enhanced by substrates such as acetoacetate, which cause oxidation of intra-mitochondrial NADH (ref. 10). In mitochondria from other tissues, such as heart and brain^8,9, the ruthenium red-insensitive release is dependent on Na⁺ ions. We report here, using mitochondria from both rat liver and brain, that nupercaine and tetracaine, at concentrations which do not inhibit Ca²⁺ uptake, cause considerable inhibition of the ruthenium red-insensitive Ca²⁺ efflux observed in energised conditions.