Both the manipulation of cholesterol and the lipid constituents of the membrane environment are known to modulate the ethanol effect on the mammalian BK (KCNMA1/Slo1) potassium channel, an ethanol target protein[14], [17], [25]–[28]. In worms, ethanol activates SLO-1 in vivo, causing a large efflux of potassium ions, hyperpolarizing the cell and depressing neuronal excitability, which is a major cause of intoxication in C. elegans [29]. The mammalian BK channel is also activated by ethanol, and this effect, as well as the channel’s basal activity, depends on the thickness of the lipid bilayer; channels that reside in thicker membrane are less basally active and are less activated by ethanol [17], [28], suggesting that movement of the BK channel into and out of areas of thicker membrane microenvironments may allow for very fast modulation of the effects of ethanol on this channel [28]. We hypothesized that this may be one mechanism by which worms develop AFT to ethanol. If AFT requires modulation of SLO-1 function, then complete loss of SLO-1 should reduce or eliminate the development of tolerance. In an otherwise wild-type
