Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals

Nora Lenkey, Tekla Kirizs, Noemi Holderith, Zoltán Máté, Gábor Szabó, E. Sylvester Vizi, Norbert Hájos, Zoltan Nusser

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Abstract

The release of GABA from cholecystokinin-containing interneurons is modulated by type-1 cannabinoid receptors (CB1). Here we tested the hypothesis that the strength of CB1 -mediated modulation of GABA release is related to the CB1 content of axon terminals. Basket cell boutons have on average 78% higher CB1 content than those of dendritic-layer-innervating (DLI) cells, a consequence of larger bouton surface and higher CB1 density. The CB1 antagonist AM251 caused a 54% increase in action potential-evoked [Ca2+ ] in boutons of basket cells, but not in DLI cells. However, the effect of AM251 did not correlate with CB1 immunoreactivity of individual boutons. Moreover, a CB1 agonist decreased [Ca2+ ] in a cell type- and CB1 -content-independent manner. Replica immunogold labelling demonstrated the colocalization of CB1 with the Cav2.2 Ca2+ channel subunit. Our data suggest that only a subpopulation of CB1 s, within nanometre distances from their target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of GABA release.

Original languageEnglish
Article number6557
JournalNature communications
Volume6
DOIs
Publication statusPublished - Apr 20 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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