LACTATE-PROTON COTRANSPORT AND ITS CONTRIBUTION TO INTERSTITIAL ACIDIFICATION DURING HYPOXIA IN ISOLATED RAT SPINAL ROOTS

Exposure of nervous tissue to hypoxia results in interstitial acidific ation. There is evidence for concomitant decrease in extracellular pH to the increase in tissue lactate. In the present study, we used doubl e-barrelled pH-sensitive microelectrodes to investigate the link betwe en lactate transport and acid-base homeostasis in isolated rat spinal roots. Addition of different organic anions to the bathing solution at constant bath pH caused transient alkaline shifts in extracellular pH ; withdrawal of these compounds resulted in transient acid shifts in e xtracellular pH. With high anion concentrations (30 mM), the largest c hanges in extracellular pH were observed with propionate > L-lactate a lmost-equal-to pyruvate > 2-hydroxy-2-methylpropionate. Changes in ext racellular pH induced by 10 mM L- and D-lactate were of similar size. Lactate transport inhibitors alpha-cyano-4-hydroxycinnamic acid and 4, 4'-dibenzamidostilbene-2,2'-disulphonic acid significantly reduced L-l actate-induced extracellular pH shifts without affecting propionate-in duced changes in extracellular pH. Hypoxia produced an extracellular a cidification that was strongly reduced in the presence of a-cyano-4-hy droxycinnamic acid and 4,4'-dibenzamidostilbene-2,2'-disulphonic acid. In contrast, amiloride and 4,4'-di-isothiocyanostilbene-2,2'-disulpho nate were without effect on hypoxia-induced acid shifts. The results i ndicate the presence of a lactate-proton co-transporter in rat periphe ral nerves. This transport system and not Na+/H+ or Cl-/HCO3- exchange seems to be the dominant mechanism responsible for interstitial acidi fication during nerve hypoxia.