Lactate-proton co-transport and its contribution to interstitial acidification during hypoxia in isolated rat spinal roots

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 ≈
pyruvate >62; 2-hydroxy-2-methylpropionate. Changes in
extracellular pH induced by 10 mMl- andd-lactate were of similar
size. Lactate transport inhibitors α-cyano-4-hydroxycinnamic acid
and 4,4′-dibenzamidostilbene-2,2′-disulphonic acid significantly
reducedl-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 α-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 C1−/HCO−3 exchange
seems to be the dominant mechanism responsible for interstitial
acidification during nerve hypoxia.