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TGFbeta2 mediates rapid inhibition of calcium influx in identified cholinergic basal forebrain neurons
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research.
2002 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 290, no 4, 1321-1327 p.Article in journal (Refereed) Published
Abstract [en]

Transforming growth factors betas (TGFbetas) are known to have important roles in neuronal survival and can be upregulated in disease. However, unlike many other trophic factors, nothing is known about the rapid neurotransmitter-like actions of TGFbeta in the CNS. We explored this by examining the effects of TGFbeta on calcium influx of large enzymatically dissociated basal forebrain neurons. We show that brief application of TGFbeta2, but not TGFbeta1, to fura-2AM-loaded neurons reversibly and acutely (within seconds) inhibited K(+)-evoked calcium influx. Moreover, using single-cell RT-PCR, we confirmed that the large TGFbeta2-responsive neurons presented a cholinergic phenotype. Investigation of the signaling mechanism underlying TGFbeta2 actions using whole-cell recordings of calcium currents revealed that TGFbeta2-mediated responses were insensitive to the nonhydrolyzable GTP analogue GTPgammaS. However, TGFbeta2-mediated calcium current reductions were prevented by intracellular perfusion of a Smad2/3 peptide antagonist. Together, these results suggest that TGFbeta2 can acutely regulate the excitability of basal forebrain cholinergic neurons through an atypical signaling mechanism.

Place, publisher, year, edition, pages
2002. Vol. 290, no 4, 1321-1327 p.
Keyword [en]
Animals, Base Sequence, Calcium Signaling/*drug effects, Choline O-Acetyltransferase/genetics, Cholinergic Fibers/drug effects/metabolism, DNA; Complementary/genetics, Glutamate Decarboxylase/genetics, Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology, Isoenzymes/genetics, Neurons/*drug effects/*metabolism, Prosencephalon/drug effects/metabolism, Rats, Rats; Sprague-Dawley, Second Messenger Systems, Transforming Growth Factor beta/*pharmacology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-10423DOI: 10.1006/bbrc.2002.6351PubMedID: 11812008OAI: oai:DiVA.org:uu-10423DiVA: diva2:38191
Available from: 2007-03-22 Created: 2007-03-22 Last updated: 2013-11-21Bibliographically approved

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Publisher's full textPubMedhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=11812008&dopt=Citation

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Souchelnytskyi, Serhiy
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