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Chunk #18 — 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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There is evidence that lipid composition is altered by alcohol exposure in biological membranes. Both acute and chronic alcohol exposures change lipid content, particularly cholesterol, in cells. One hour of alcohol exposure depletes plasma cholesterol [61], presumably also decreasing membrane-bound cholesterol, making membranes more fluid or disordered [61]. By contrast, after days-long exposure to alcohol, cellular membranes become tolerant to the disordering effects of alcohol (so-called ‘membrane tolerance’), responding with alterations in specific phospholipids, such as cardiolipin and phosphatidylinositol [62]. Thus, experiments with BK provide ample evidence of the powerful effects that lipid environment can have in both the immediate and adaptive response to alcohol. However, it is important to note that this line of investigation provides at this time the potential for a major mediator of alcohol tolerance (e.g. that BK might move into and out of lipid rafts, thereby changing both the acute response and adaptation to alcohol). Further research must be performed to better understand whether these mechanisms are, indeed, playing a role in addictive behaviors.