title: T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle.
abstract: We have studied lactic acid transport in the fast mouse extensor digitorum longus muscles (EDL) by intracellular and cell surface pH microelectrodes. The role of membrane-bound carbonic anhydrases (CA) of EDL in lactic acid transport was investigated by measuring lactate flux in muscles from wildtype, CAIV-, CAIX- and CAXIV-single ko, CAIV-CAXIV double ko and CAIV-CAIX-CAXIV-triple ko mice. This was complemented by immunocytochemical studies of the subcellular localization of CAIV, CAIX and CAXIV in mouse EDL. We find that CAXIV and CAIX single ko EDL exhibit markedly but not maximally reduced lactate fluxes, whereas triple ko and double ko EDL show maximal or near-maximal inhibition of CA-dependent lactate flux. Interpretation of the flux measurements in the light of the immunocytochemical results leads to the following conclusions. CAXIV, which is homogeneously distributed across the surface membrane of EDL fibers, facilitates lactic acid transport across this membrane. CAIX, which is associated only with T tubular membranes, facilitates lactic acid transport across the T tubule membrane. The removal of lactic acid from the lumen of T tubuli towards the interstitial space involves a CO2-HCO3- diffusional shuttle that is maintained cooperatively by CAIX within the T tubule and, besides CAXIV, by the CAIV, which is strategically located at the opening of the T tubules. The data suggest that about half the CA-dependent muscular lactate flux occurs across the surface membrane, while the other half occurs across the membranes of the T tubuli.
authors.affiliation: Molecular and Cell Physiology, Vegetative Physiologie, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Hallerdei
authors.forename: Renate J
authors.initials: RJ
authors.lastname: Scheibe
authors.forename: Seppo
authors.initials: S
authors.lastname: Parkkila
authors.forename: Abdul
authors.initials: A
authors.lastname: Waheed
authors.forename: William S
authors.initials: WS
authors.lastname: Sly
authors.forename: Gerolf
authors.initials: G
authors.lastname: Gros
authors.forename: Petra
authors.initials: P
authors.lastname: Wetzel
authors.forename: Volker
authors.initials: V
authors.lastname: Endeward
mesh_terms: D000818:Animals; D001692:Biological Transport; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D004566:Electrodes; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008954:Models, Biological; D027501:Monocarboxylic Acid Transporters / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D009132:Muscles
chemical_list: D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; C498648:Slc16a4 protein, mouse; D019344:Lactic Acid; D002256:Carbonic Anhydrases