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 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.
Schneider
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U
Department of Physiology, University of Munich, Germany.
Poole
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RC
Halestrap
A P
AP
Grafe
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P
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives; D000138:Acidosis / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D003373:Coumaric Acids; D005110:Extracellular Space / Q000378:metabolism / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D008839:Microelectrodes; D027501:Monocarboxylic Acid Transporters; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D011522:Protons; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
D002352:Carrier Proteins; D003373:Coumaric Acids; D007773:Lactates; D027501:Monocarboxylic Acid Transporters; D011522:Protons; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C007175:alpha-cyano-4-hydroxycinnamate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid