title: Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals.
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 [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.
authors.affiliation: Lendület Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: Nora
authors.initials: N
authors.lastname: Lenkey
authors.affiliation: 1] Lendület Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary [2] János Szentágothai School of Neurosciences, Semmelweis University, Budapest H1085, Hungary.
authors.forename: Tekla
authors.initials: T
authors.lastname: Kirizs
authors.affiliation: Lendület Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: Noemi
authors.initials: N
authors.lastname: Holderith
authors.affiliation: Division of Medical Gene Technology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Máté
authors.affiliation: Division of Medical Gene Technology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Laboratory of Drug Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: E Sylvester
authors.initials: ES
authors.lastname: Vizi
authors.affiliation: Lendület Laboratory of Network Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Szigony street 43, Budapest H1083, Hungary.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hájos
authors.affiliation: Lendület Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H1083, Hungary.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Nusser
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification; D017729:Presynaptic Terminals / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D002118:Calcium; D063388:Endocannabinoids; D008164:Luminescent Proteins; D043884:Receptor, Cannabinoid, CB1; D005680:gamma-Aminobutyric Acid; D000097573:Red Fluorescent Protein