Effect of 2,6-diisopropylphenol and halogenated anesthetics on tetraphenylphosphonium uptake by rat brain synaptosomes: Determination of membrane potential

The effect of 2,6-diisopropylphenol (propofol) in comparison to that of the halogenated anesthetics enflurane, isoflurane, and halothane on tetrapenyl phosphonium uptake by rat brain synaptosomes was studied. A direct method t o separately measure the synaptosomal and the mitochondrial transmembrane p otential by using the tetraphenylphosphonium cation (TPP+) was utilized. Th e latter is a lipophylic charged molecule which distributes between two com partments according to the transmembrane electrical potential in the presen ce or absence of 60 mM KCl as a synaptosomal membrane depolarizing agent. A fter previously reporting the damages induced by general anesthetics on iso lated mitochondria, the aim of this paper was to study their possible actio n on the synaptosomal membrane potential and whether or not drugs concentra tions damaging isolated mitochondria are also effective on synaptosomal mit ochondria. The results indicated that, in the presence of glucose, mitochon dria included in synaptosomes were able to maintain a transmembrane potenti al of 202 +/- 8 mV (mean +/- SD) while the synaptosomal membrane showed a p otential of 78 +/- 8 mV (mean +/- SD). When anesthetic concentrations (0.6- 1 mM propofol, 10-40 mu M enflurane, 30-50 mu M isoflurane, 8-15 mu M halot hane) that impair mitochondrial energy metabolism were used, the synaptosom al transmembrane potential was maintained and, in addition, a slight increa se of the TPP+ taken up was observed as the anesthetic concentration was in creased.