Zelluläre Protonen-Pufferung: Räumlich-zeitliche Dynamik

• Antragsteller: Professor Dr. Joachim W. Deitmer
• Fachliche Zuordnung: Molekulare Biologie und Physiologie von Nerven- und Gliazellen
• Förderung: Förderung von 2009 bis 2017
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 155896687

• Erstellungsjahr: 2017

Zusammenfassung der Projektergebnisse

We have used mammalian astrocytes in vitro and in situ and Xenopus oocytes to study the role of various acid/base membrane carriers for H+ buffering and regulation. In particular focus was the electrogenic sodium-bicarbonate cotransporter NBCe1, its functional diversity and regulation of expression. Our results indicate that functional NBCe1 expression in the astrocyte membrane is strictly regulated and operates as the main intracellular pH regulator in these cells. We found that NBCe1 activity plays an important role for physiological H+ buffering in astrocytes and for pH-dependent processes such as energy metabolism, including glycolysis. We conclude that astrocytes are bicarbonate sensors in the brain, mediated by NBCe1 and carbonic anhydrase activity. Both proteins are also supportive of lactate transport in astrocytes as carried out by different monocarboxylate transporter isoforms (MCT1, MCT4).

Projektbezogene Publikationen (Auswahl)

• (2013) GPI-anchored carbonic anhydrase isoform IV displays extraand intracellular catalytic activity both in cRNA-injected oocytes and in mouse neurons. Proc. Natl. Acad. Sci. USA 110, 1494-1499
  Schneider, H.P., Alt, M.D., Klier, M., Spiess, A., Andes, F.T., Waheed, A., Sly, W.S., Becker, H.M. & Deitmer, J.W.
  
• (2013) Physiology of astrocytes: Ion channels and ion transporters. In: Neuroglia (eds. H. Kettenmann & B.R. Ransom), Oxford University Press, p. 185-196
  Steinhäuser, C., Seifert, G. & Deitmer, J.W.
  
• (2014) The electrogenic sodium-bicarbonate cotransporter NBCe1 is a high-affinity bicarbonate carrier in mouse cortical astrocytes. J. Neurosci. 34, 1148-1157
  Theparambil, M.S., Ruminot, I., Schneider, H.P., Shull, G.E. & Deitmer, J.W.
  
• (2015) Catalytic activity of human carbonic anhydrase IX is displayed extra- and intracellularly. FEBS J. 283, 191-200
  Klier, M, Jamali, S., Ames, S. Schneider, H.P., Becker, H.M. & Deitmer, J.W.
  
• (2015) The role of membrane acid/base transporters and carbonic anhydrases for cellular pH and metabolic processes. Front. Neurosci. 8:430
  Deitmer, J.W., Theparambil, S.M., Ruminot I. & Becker, H.M.
  
• (2015). High effective cytosolic H+ buffering in mouse cortical astrocytes attributable to fast bicarbonate transport. Glia 63, 1581-1594
  Theparambil, S.M. & Deitmer, J.W.
  
• (2016) Proton or bicarbonate: Glycolytic rate in mouse cortical astrocytes is paved by intracellular alkalinization. J. Biol Chem. 291, 19108-19117
  Theparambil, S.M., Weber, T., Schmälzle, J., Ruminot, I., Deitmer, J.W.
  
• (2017) Bicarbonate sensing in mouse cortical astrocytes during acid/base disturbances. J. Physiol. 595, 2569-2585
  Theparambil, S.M., Naoshin, Z., Defren, S., Schmälzle, J., Weber, T., Schneider, H.P. & Deitmer, J.W.