Specific Modulation of two Neuronal Digitalis Receptors by Anaesthesia

Abstract

Three isoenzymes of digitalis receptors (α1, α2, α3) in the brain and only one in the kidney (α1) can be distinguished by their ouabain affinities and their responsiveness to sodium. Since we have reported modulations for these digitalis receptors by their fatty acid membrane environment, anaesthesics could bind on and modulate either directly these receptors or indirectly by disturbing membrane lipids. The aim of this study was to evaluate this anaesthetic action on apparent ouabain affinities and sodium dependence of cerebral and renal Na+,K+-ATPase isoenzymes activities. Rat brain and kidney membrane fractions with pentobarbital-induced anaesthetized state were compared to an unanaesthetized state for their (1) fatty acid composition of total membrane phospholipids, (2) responsiveness to ouabain and (3) Na+ dependence of digitalis receptors. An anaesthesia period of 10 minutes induced (1) a fatty acid modification of brain membranes and (2) a significant sensibilization to ouabain for the α2 and α3 isoforms of digitalis receptors (α2, IC50; 8.2 ± 0.5 × 107 mol/l vs 4.5±0.2 × 107 mol/l; α3, IC50; 6.0±0.3 × 10-8 mol/l vs 2.5±0.1 × 10-8 mol/l). In contrast, the ouabain affinity of the α1 subunit expressed in kidney and brain membranes was unaltered. No anaesthetic effect was observed on the Na+ dependence of the α1 isoenzyme in the brain (4 mmol/l) and the kidney (8 mmol/l). Pentobarbital induced a desensibilization for α2-receptors (8.3±0.5 vs 16.0±1.4 mmol/l Na+) and a sensibilization for α3-receptors (14.4±0.8 vs 10±1.3 mmol/l Na+). These altered properties could be related to a selective modification of the fatty acid composition and/or to the presence of a specific binding site for pentobarbital on these two neuronal digitalis receptors.