title: Excitability of prefrontal cortical pyramidal neurons is modulated by activation of intracellular type-2 cannabinoid receptors.
abstract: The endocannabinoid (eCB) system is widely expressed throughout the central nervous system (CNS) and the functionality of type-1 cannabinoid receptors in neurons is well documented. In contrast, there is little knowledge about type-2 cannabinoid receptors (CB(2)Rs) in the CNS. Here, we show that CB(2)Rs are located intracellularly in layer II/III pyramidal cells of the rodent medial prefrontal cortex (mPFC) and that their activation results in IP(3)R-dependent opening of Ca(2+)-activated Cl(-) channels. To investigate the functional role of CB(2)R activation, we induced neuronal firing and observed a CB(2)R-mediated reduction in firing frequency. The description of this unique CB(2)R-mediated signaling pathway, controlling neuronal excitability, broadens our knowledge of the influence of the eCB system on brain function.
authors.affiliation: Center for Neuroscience, Swammerdam Institute for Life Sciences,  University of Amsterdam, 1098 XH, Amsterdam,  The Netherlands.
authors.forename: Femke S
authors.initials: FS
authors.lastname: den Boon
authors.forename: Pascal
authors.initials: P
authors.lastname: Chameau
authors.forename: Qiluan
authors.initials: Q
authors.lastname: Schaafsma-Zhao
authors.forename: Willem
authors.initials: W
authors.lastname: van Aken
authors.forename: Monica
authors.initials: M
authors.lastname: Bari
authors.forename: Sergio
authors.initials: S
authors.lastname: Oddi
authors.forename: Chris G
authors.initials: CG
authors.lastname: Kruse
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.forename: Wytse J
authors.initials: WJ
authors.lastname: Wadman
authors.forename: Taco R
authors.initials: TR
authors.lastname: Werkman
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology; D018118:Chloride Channels / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology* / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology
chemical_list: D002186:Cannabinoids; D018118:Chloride Channels; C469526:Cnr2 protein, rat; C571734:N-(1-(4-((4-chloro-2-((2-fluorophenyl)sulfonyl)phenyl)sulfonyl)phenyl)ethyl)methanesulfonamide; D043885:Receptor, Cannabinoid, CB2; D013449:Sulfonamides; D013450:Sulfones; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC