Nemzeti Kutatási és Technológiai Hivatal(P2012-23,)
OMFB(01678/2009)
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 [Ca(2+)] 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
[Ca(2+)] in a cell type- and CB1-content-independent manner. Replica immunogold labelling
demonstrated the colocalization of CB1 with the Cav2.2 Ca(2+) channel subunit. Our
data suggest that only a subpopulation of CB1s, within nanometre distances from their
target Cav2.2 channels, are responsible for endocannabinoid-mediated modulation of
GABA release.
