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Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice.
Sci Rep. 2016 08 04; 6:30857.SR

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+Show Affiliations

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.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 Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji City, Jilin Province, 133002, China.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27489024

Citation

Wu, Mao-Cheng, et al. "Ethanol Modulates Facial Stimulation-evoked Outward Currents in Cerebellar Purkinje Cells in Vivo in Mice." Scientific Reports, vol. 6, 2016, p. 30857.
Wu MC, Bing YH, Chu CP, et al. Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice. Sci Rep. 2016;6:30857.
Wu, M. C., Bing, Y. H., Chu, C. P., & Qiu, D. L. (2016). Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice. Scientific Reports, 6, 30857. https://doi.org/10.1038/srep30857
Wu MC, et al. Ethanol Modulates Facial Stimulation-evoked Outward Currents in Cerebellar Purkinje Cells in Vivo in Mice. Sci Rep. 2016 08 4;6:30857. PubMed PMID: 27489024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol modulates facial stimulation-evoked outward currents in cerebellar Purkinje cells in vivo in mice. AU - Wu,Mao-Cheng, AU - Bing,Yan-Hua, AU - Chu,Chun-Ping, AU - Qiu,De-Lai, Y1 - 2016/08/04/ PY - 2016/03/29/received PY - 2016/07/08/accepted PY - 2016/8/5/entrez PY - 2016/8/5/pubmed PY - 2018/5/1/medline SP - 30857 EP - 30857 JF - Scientific reports JO - Sci Rep VL - 6 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/27489024/Ethanol_modulates_facial_stimulation_evoked_outward_currents_in_cerebellar_Purkinje_cells_in_vivo_in_mice_ L2 - https://doi.org/10.1038/srep30857 DB - PRIME DP - Unbound Medicine ER -