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coga / coga-kb
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Chunk #3 — Introduction

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Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol.
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We investigated whether alcohol, via miRNA, can regulate expression and stability of alternatively spliced mRNAs encoding the main, pore forming α subunit of the BK channel, a large conductance calcium- and voltage-activated potassium channel (Slowpoke, BK, MaxiK), which is a product of the KCNMA1 gene. The BK channel (Atkinson et al., 1991) is widely expressed in brain (Knaus et al., 1996; Misonou et al., 2006; Wanner et al., 1999), and influences neuronal excitability, firing frequency and transmitter release (Storm, 1990). Alternatively spliced variants of the α subunit, and their assembly into functional tetramers contributes to functional diversity of the BK channel (Adelman et al., 1992;Atkinson et al., 1991;Butler et al., 1993;Lagrutta et al., 1994;Navaratnam et al., 1997;Rosenblatt et al., 1997;Shipston, 2001;Tseng-Crank et al., 1994) in the brain (Ha et al., 2000; MacDonald et al., 2006). Alternative splicing of BK is dynamically regulated, e.g., the inclusion of the STREX exon is determined by neuronal activity or stress (Xie and McCobb, 1998).