Profound effects of the general anesthetic etomidate on oxidative phosphorylation without effects on their yield.
We investigated the effects of the general anesthetic Etomidate on oxidative phosphorylation in isolated rat liver mitochondria. The study of each electron transfer site shows that there is an inhibition: mainly at complex I but also, to a lesser extent, at complex III. Moreover, with succinate as substrate, the increase in non-phosphorylating respiration is accompanied by a decrease in DeltaPsi. However, this effect is not due to classical uncoupling of oxidative phosphorylation, since ADP addition at high Etomidate concentrations restores the transmembrane difference of electrical potential. Also, in the same range of Etomidate concentration, the ATP/O ratio is not significantly affected. In conclusion, the main effect of Etomidate is to decrease the oxidative phosphorylation rate without changing yield. The H(+) leak which appears under non-phosphorylating conditions becomes negligible in physiological conditions.
Devin
Anne
A
Institut de Biochimie et Génétique Cellulaires du CNRS, Université de BordeauxII, 1 rue Camille Saint-Saëns, 33077, Bordeaux cedex, France.
Nogueira
Véronique
V
Avéret
Nicole
N
Leverve
Xavier
X
Rigoulet
Michel
M
D000244:Adenosine Diphosphate / Q000378:metabolism; D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D042967:Electron Transport Complex I / Q000187:drug effects / Q000502:physiology; D014450:Electron Transport Complex III / Q000187:drug effects / Q000502:physiology; D005045:Etomidate / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology*; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000502:physiology; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000378:metabolism
D018681:Anesthetics, General; D000244:Adenosine Diphosphate; D019802:Succinic Acid; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005045:Etomidate