Moreover, additional upstream pathways, specifically regulating transcription of BK gene expression (Figure 8) might be involved after longer alcohol exposures. Previous studies of regulation of BK channel alternative splicing by e.g. stress or activity (McCobb et al., 2003;Xie and McCobb, 1998) have focused on splicing decisions during production of pre-mRNA from the gene, with a time frame of weeks. Recently, it has been discovered that BK channel transcription is under epigenetic control (Wang et al., 2007). Could alcohol act via a similar mechanism and could miRNA be involved? For example, alcohol might modulate alternative splicing during transcription and pre-mRNA exonal assembly, skipping the ALCOREX exon and excluding it from the final variants of BK mRNA. Considering the length of the BK gene (~ 690 kb, AC 000083) and the elongation rate of polymerase II (~30 nt/sec, Alberts et al., 1994), 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
