title: Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice.
abstract: Acute ethanol overdose can induce dysfunction of cerebellar motor regulation and cerebellar ataxia. In this study, we investigated the effect of ethanol on facial stimulation-evoked inhibitory synaptic responses in cerebellar Purkinje cells (PCs) in urethane-anesthetized mice, using in vivo patch-clamp recordings. Under voltage-clamp conditions, ethanol (300 mM) decreased the amplitude, half-width, rise time and decay time of facial stimulation-evoked outward currents in PCs. The ethanol-induced inhibition of facial stimulation-evoked outward currents was dose-dependent, with an IC50 of 148.5 mM. Notably, the ethanol-induced inhibition of facial stimulation-evoked outward currents were significantly abrogated by cannabinoid receptor 1 (CB1) antagonists, AM251 and O-2050, as well as by the CB1 agonist WIN55212-2. Moreover, the ethanol-induced inhibition of facial stimulation-evoked outward currents was prevented by cerebellar surface perfusion of the PKA inhibitors H-89 and Rp-cAMP, but not by intracellular administration of the PKA inhibitor PKI. Our present results indicate that ethanol inhibits the facial stimulation-evoked outward currents by activating presynaptic CB1 receptors via the PKA signaling pathway. These findings suggest that ethanol overdose impairs sensory information processing, at least in part, by inhibiting GABA release from molecular layer interneurons onto PCs.
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji City, Jilin Province, 133002, China.|Department of osteology, Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, 133000, China.
authors.forename: Mao-Cheng
authors.initials: MC
authors.lastname: Wu
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji City, Jilin Province, 133002, China.|Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, 133002, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Bing
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji City, Jilin Province, 133002, China.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Chu
authors.affiliation: Key Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji City, Jilin Province, 133002, China.|Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji City, Jilin Province, 133002, China.|Key Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular of the Ministry of Education, Yanbian University, Yanji City, Jilin Province, 133002, China.
authors.forename: De-Lai
authors.initials: DL
authors.lastname: Qiu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation / Q000379:methods; D010880:Piperidines / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*; D012018:Reflex / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C508712:(6aR,10aR)-3-(1-methansulfonylamino-4-hexyn-6-yl)6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo(b,d)pyran; D048588:Benzoxazines; D002492:Central Nervous System Depressants; D007546:Isoquinolines; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011714:Pyrans; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C103505:AM 251; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D013759:Dronabinol; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide