diversity of proteins [67], and enabling cells to adapt to various environmental cues. Particularly relevant to this review are recent studies on mRNAs encoding N-type calcium channels in PC12 cells [68] and in vivo rat glutamate receptor NMDAR1(N- methyl d-aspartic acid receptor 1) subunit [69] demonstrating that alternative splicing can be modulated by alcohol and that alternatively spliced isoforms can differ in their alcohol sensitivity. BK channel alternative splicing has been extensively characterized [13]. In a novel example of an epigenetic mechanism of molecular tolerance, rat brain miR-9, a representative of the recently discovered class of microRNA molecules, is upregulated by alcohol exposure (Figure 3), leading to the selective destruction of those isoforms of the BK channel exhibiting the highest sensitivity to alcohol, while sparing those isoforms that exhibit lower sensitivity. This occurs within minutes of exposure. Thus, these neurons have evolved an elegant mechanism whereby BK function (although compromised) remains, whereas the dysfunction attributable to effects of alcohol on the channel are minimized. Certainly, the evolutionary pressure leading to this strategy is of great interest. One can envision a range of possibilities, from adaptation as a means of protection from intoxicating levels of ingested alcohol from sources, such as
