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Alcohol Regulation of BK Channels Surface Expression via Beta‐Catenin Signaling
Author(s) -
Garcia Jose Orlando,
Burgos Alexandra,
Soto Jessica,
Cordero Katherine,
Treistman Steven,
VelazquezMarrero Cristina
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb697
Subject(s) - internalization , chemistry , bk channel , wnt signaling pathway , western blot , hek 293 cells , microbiology and biotechnology , immunoprecipitation , biochemistry , signal transduction , biology , cell , membrane potential , gene
Alcohol tolerance development and retention has long been associated to neural mechanisms related to learning and memory. We have found a persistent component of alcohol molecular tolerance; internalization of BK channels, in both striatal and hippocampus neurons. It is further characterized by increases in β‐catenin in response to physiologically relevant concentrations of alcohol, which are necessary for BK channel internalization. Accumulation of β‐catenin was impaired in the presence of general protein synthesis inhibitors cyclohexamide and emetine, which further blocked ethanol‐induced BK channel internalization in heterologous expression system. Interestingly, BK channel dissociation from lipid raft fractions in response to ethanol exposure was not significantly affected by protein synthesis inhibition. Translational regulation of EtOH was evaluated via tandem mass spectrometry (MS/MS) and Western Blot analysis of de novo synthesized proteins in heterologously expressed hSloα HEK293 preparations. Results indicated that β‐catenin is increased 2.5 fold in response to alcohol compared within a subset of over seven hundred proteins assayed. Transcriptional regulation of EtOH in striatal tissue has been further studied suggesting changes in miRNA profile in response to duration of EtOH exposure. These findings suggest the canonical Wnt/β‐catenin signaling pathway plays a critical role in mediating a persistent form of BK channel molecular alcohol tolerance regulating BK channel surface distribution, and potentially mediating transcriptional regulation in response to EtOH. Support or Funding Information This work was supported by the COBRE project grant 5P20GM103642 (CV‐M), Imaging core at the Institute of Neurobiology: NSF Grant DBI‐0115825 and DoD Grant 52680‐LS‐IS, Research infrastructure support was provided in part by a grant from the National Institute of Minority Health and Health Disparities (G12MD 007600), and USDE Title V Cooperative Agreement grant P031S130068 (JOG).