t tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal musclet管和表面膜提供同样的有效途径碳酸anhydrase-facilitated骨骼肌乳酸运输.pdfVIP

T Tubules and Surface Membranes Provide Equally Effective Pathways of Carbonic Anhydrase-Facilitated Lactic Acid Transport in Skeletal Muscle 1 2 3 4 4 1 Janine Hallerdei , Renate J. Scheibe , Seppo Parkkila , Abdul Waheed , William S. Sly , Gerolf Gros *, 1 1 Petra Wetzel , Volker Endeward * 1 Molecular and Cell Physiology, Vegetative Physiologie, Medizinische Hochschule Hannover, Hannover, Germany, 2 Abteilung Physiologische Chemie, Medizinische Hochschule Hannover, Hannover, Germany, 3 Institute of Medical Technology, Tissue Biology, University of Tampere, Tampere, Finland, 4 Department of Biochemistry and Molecular Biology, St. Louis University, St. Louis, Missouri, United States of America 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 E