Exposure of nervous tissue to
hypoxia results in interstitial acidification. There is evidence for concomitant decrease in extracellular pH to the increase in tissue
lactate. In the present study, we used double-barrelled pH-sensitive
microelectrodes to investigate the link between
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 extracellular pH. With high
anion concentrations (30 mM), the largest changes in extracellular pH were observed with
propionate > L-
lactate approximately
pyruvate > 2-hydroxy-2-methylpropionate. Changes in extracellular 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-
lactate-induced extracellular pH shifts without affecting
propionate-induced changes in extracellular pH.
Hypoxia produced an extracellular acidification that was strongly reduced in the presence of
alpha-cyano-4-hydroxycinnamic acid and 4,4'-dibenzamidostilbene-2,2'-disulphonic
acid. In contrast,
amiloride and 4,4'-di-isothiocyanostilbene-2,2'-disulphonate were without effect on
hypoxia-induced
acid shifts. The results indicate the presence of a
lactate-
proton co-transporter in rat peripheral nerves. This transport system and not Na+/H+ or Cl-/HCO3- exchange seems to be the dominant mechanism responsible for interstitial acidification during nerve
hypoxia.