Relief of G-protein inhibition of calcium channels and short-term synaptic facilitation in cultured hippocampal neurons

David L. Brody, David T. Yue

Research output: Contribution to journalArticle

Abstract

G-protein inhibition of voltage-gated calcium channels can be transiently relieved by repetitive physiological stimuli. Here, we provide evidence that such relief of inhibition contributes to short-term synaptic plasticity in microisland-cultured hippocampal neurons. With G-protein inhibition induced by the GABA(B) receptor agonist baclofen or the adenosine A1 receptor agonist 2-chloroadenosine, short-term synaptic facilitation emerged during action potential trains. The facilitation decayed with a time constant of ~100 msec. However, addition of the calcium channel inhibitor Cd2+ at 2-3 μM had no such effect and did not alter baseline synaptic depression. As expected of facilitation from relief of channel inhibition, analysis of miniature EPSCs implicated presynaptic modulation, and elevating presynaptic Ca2+ entry blunted the facilitation. Most telling was the near occlusion of synaptic facilitation after selective blockade of P/Q- but not N-type calcium channels. This was as predicted from experiments using recombinant calcium channels expressed in human embryonic kidney (HEK) 293 cells; we found significantly stronger relief of G-protein inhibition in recombinant P/Q- versus N-type channels during action potential trains. G- protein inhibition in HEK 293 cells was induced via recombinant M2 muscarinic acetylcholine receptors activated by carbachol, an acetylcholine analog. Thus, relief of G-protein inhibition appears to produce a novel form of short-term synaptic facilitation in cultured neurons. Similar short-term synaptic plasticity may be present at a wide variety of synapses, as it could occur during autoreceptor inhibition by glutamate or GABA, heterosynaptic inhibition by GABA, tonic adenosine inhibition, and in many other instances.

Original languageEnglish (US)
Pages (from-to)889-898
Number of pages10
JournalJournal of Neuroscience
Volume20
Issue number3
StatePublished - Feb 1 2000

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Calcium Channels
GTP-Binding Proteins
Neurons
Neuronal Plasticity
gamma-Aminobutyric Acid
Action Potentials
Adenosine A1 Receptor Agonists
N-Type Calcium Channels
GABA-B Receptor Agonists
2-Chloroadenosine
Kidney
Autoreceptors
Baclofen
Carbachol
Muscarinic Receptors
Adenosine
Synapses
Acetylcholine
Glutamic Acid

Keywords

  • Adenosine
  • Autapses
  • Baclofen
  • Calcium channels
  • Cultured neurons
  • Facilitation
  • G-protein inhibition
  • GABA
  • HEK 293 cells
  • Hippocampal neurons
  • Microcultures
  • Recombinant calcium channels
  • Short-term synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Relief of G-protein inhibition of calcium channels and short-term synaptic facilitation in cultured hippocampal neurons. / Brody, David L.; Yue, David T.

In: Journal of Neuroscience, Vol. 20, No. 3, 01.02.2000, p. 889-898.

Research output: Contribution to journalArticle

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