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Chunk #52 — Discussion — microRNA involvement in mechanisms of tolerance

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Posttranscriptional regulation of BK channel splice variant stability by miR-9 underlies neuroadaptation to alcohol.
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production of modified BK transcripts would be expected to take at least 6 hours. Indeed, our data indicate the augmentation of tolerance after at least 6 hours of exposure (Figure 7D). It has recently been shown also that another microRNA species (miR-133) can regulate alternative splicing during gene transcription in muscle (Boutz et al., 2007). We also observed that in HEK cells, which lack miR-9, several hours of alcohol exposure decreases BK current density in the plasma membrane (data not shown). Therefore, it is possible that for longer alcohol exposures, additional mechanisms of gene expression, possibly including other miRNA species, could be regulated by alcohol.