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Chunk #14 — Lipid environment affects the immediate and long-term response of BK to alcohol

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BK Channels: mediators and models for alcohol tolerance.
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An intriguing finding from the standpoint of lipid modulation of the ethanol response and adaptation of BK channels derives from the manipulation of bilayer thickness, which can have particular importance in light of evidence for the presence of lipid rafts. Rafts are membrane domains enriched in cholesterol and sphingomyelin. In biological membranes, they are postulated to be equivalent to the liquid ordered (Lo) phase of model membranes, surrounded by a contiguous ‘sea’ of membrane with a lipid structure equivalent to the liquid disordered (Ld) phase of model membranes [50]. Cholesterol is crucial to maintain these domains in the Lo phase, which retains a high degree of acyl chain ordering, while keeping the translational disordering necessary for transmembrane proteins to maintain functional structure and conformational change [51]. Lipid rafts provide a platform for channels to assemble with signaling molecules [52–55]. Importantly, BK channels reside, at least some of the time, in lipid rafts [56]. Altering the thickness of the bilayer by adjusting the acyl chain length of the component lipids affects the time course of the acute response to alcohol and