Gap junctional control of glial glutamate transporter expression.
The uptake of glutamate into astroglia is the predominant mechanism to terminate glutamatergic neurotransmission and to prevent neurotoxic extracellular glutamate concentrations. Here, we show that uncoupling cultured cortical astrocytes with the gap junction blocker, propofol, or the Cx43 mimetic peptide, Gap27, inhibits the expression of GLT-1, the major glutamate transporter subtype in the cortex. The dependence of GLT-1 expression on gap junctions was further confirmed by the use of astrocytes in which either the expression of Cx43, the major astrocytic gap junction protein, was inhibited by RNA interference or which were derived from animals carrying an astrocyte-specific deletion of the Cx43 gene. In both cases, reduced astrocytic coupling was associated with a pronounced decline in GLT-1 expression. Finally, a luciferase reporter gene assay demonstrated that blockade of gap junctions/connexins suppressed transcriptional activity of GLT-1 promoter. These observations unravel a previously unrecognized role of gap junctions in the control of glial glutamate transport.
Figiel
Maciej
M
Institute of Anatomy, University of Leipzig, Medical Faculty, Liebigstr. 13, 04103 Leipzig, Germany.
Allritz
Claudia
C
Lehmann
Claudia
C
Engele
Jürgen
J
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018031:Connexin 43 / Q000235:genetics; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D008113:Liver Neoplasms; D008156:Luciferases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D015742:Propofol / Q000494:pharmacology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology
D000927:Anticonvulsants; D018031:Connexin 43; D027342:Excitatory Amino Acid Transporter 2; D018698:Glutamic Acid; D008156:Luciferases; D015742:Propofol