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TGFbeta2 mediates rapid inhibition of calcium influx in identified cholinergic basal forebrain neurons

Sylvain Williams1, Serhiy Souchelnytskyi, Marc Danik

  • 1Douglas Hospital Research Center, McGill University, Montreal, Quebec, Canada. wilsyl@douglas.mcgill.ca

Biochemical and Biophysical Research Communications
|January 29, 2002
PubMed

Insights

Transforming growth factor-beta 2 (TGFbeta2) rapidly inhibits calcium influx in basal forebrain cholinergic neurons. This neurotransmitter-like action occurs via an atypical Smad2/3 signaling pathway, suggesting novel roles in neuronal excitability.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Molecular Signaling

Background:

  • Transforming growth factors betas (TGFbetas) are recognized for their roles in neuronal survival.
  • Their rapid, neurotransmitter-like actions within the central nervous system (CNS) remain largely unexplored.
  • TGFbetas can be upregulated in various neurological diseases.

Purpose of the Study:

  • To investigate the acute, neurotransmitter-like effects of TGFbetas on central nervous system neurons.
  • To elucidate the specific actions of TGFbeta2 on calcium influx in basal forebrain neurons.
  • To identify the signaling mechanisms underlying TGFbeta2's rapid effects.

Main Methods:

  • Utilized fura-2AM to measure calcium influx in enzymatically dissociated basal forebrain neurons.
  • Applied TGFbeta1 and TGFbeta2 to assess their effects on potassium-evoked calcium influx.
  • Employed single-cell RT-PCR to identify neuronal phenotypes.
  • Investigated signaling pathways using whole-cell recordings of calcium currents and Smad2/3 peptide antagonists.

Main Results:

  • TGFbeta2, but not TGFbeta1, acutely and reversibly inhibited K(+)-evoked calcium influx within seconds.
  • TGFbeta2-responsive neurons were identified as having a cholinergic phenotype.
  • TGFbeta2-mediated calcium current reduction was insensitive to GTPgammaS but blocked by a Smad2/3 antagonist.

Conclusions:

  • TGFbeta2 exhibits rapid, neurotransmitter-like regulation of excitability in basal forebrain cholinergic neurons.
  • The signaling mechanism involves an atypical pathway dependent on Smad2/3.
  • These findings reveal a novel function for TGFbeta2 in modulating neuronal activity.

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