Alcohol Regulation of BK Channels Surface Expression via Beta‐Catenin Signaling
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2017
- Source ID
- 10.1096/fasebj.31.1_supplement.lb697
Entities
People
- Alexandra Burgos
- Cristina Velazquez‐marrero
- Jessica Soto
- Jose Orlando Garcia
- Katherine Cordero
- Steven Treistman
Organizations
- National Science Foundation Office of the Director
- United States Department of Defense
- University of Puerto Rico