The respiration of brain mitochondria and its regulation by monovalent cation transport.
The Na+ and K+ permeability properties of rat brain mitochondria were determined to explain the influences of these cations upon respiration. A new procedure for isolating exceptionally intact mitochondria with minimal contamination by synaptosomes was developed for this purpose. Respiration was uncoupled by Na+ and less so by K+. Uncoupling was maximal in the presence of EDTA plus Pi and was decreased by Mg2+. Maximal uncoupler-stimulated respiration rates were inhibited by Na+ but largely unaffected by K+. The inhibition by Na+ was relatively insensitive to Mg2+. Membrane Na+ and K+ conductances as well as neutral exchanges (Na+/H+ and K+/H+ antiport activities) were determined by swelling measurements and correlated with metabolic effects of the cations. Cation conductance, i.e. electrophoretic Na+ or K+ permeation, was increased by EDTA (Na+ greater than K+) and decreased by Mg2+. Magnesium preferentially suppressed Na+ conductance so as to reverse the cation selectivity (K+ greater than Na+). Neutral cation/H+ exchange rates (Na+ greater than K+) were not influenced by chelator or Mg2+. The extent of cation-dependent uncoupling of respiration correlated best with the inner membrane conductance of the ion according to an empirical relationship derived with the model K+ conductor valinomycin. The metabolic influences of Na+ and K+ can be explained in terms of coupled flow of these ions with protons and their effect upon the H+ electrochemical gradient although alternative possibilities are discussed. These in vitro studies are compared to previous observations in situ to assess their physiological significance.
D000818:Animals; D001693:Biological Transport, Active; D001921:Brain / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism* / Q000494:pharmacology
D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D004492:Edetic Acid; D012964:Sodium; D011188:Potassium