While we favor a model of a direct effect of lipid microdomains in modulation of SLO-1 activity, as is seen for mammalian SLO-1/BK channels (reviewed by Treistman and Martin [30]), the data presented here are also compatible with a model in which lipid modulation of activity of neuronal function occurs independently of SLO-1 function. For example, altering the level of TAGs might increase the excitability of cholinergic motor neurons or decrease the excitability of GABAergic motor neurons, both effects might lead to a decreased ethanol response. Loss of lips-7 function, which increases TAG levels, results in a loopy locomotion phenotype, acute ethanol resistance and a more rapid development of AFT. These phenotypes are consistent with an increase in the overall excitability of the locomotor cholinergic circuitry. However, we have shown previously with mutants that enhance the activity of the cholinergic neurons, that the degree of neuronal excitability and the degree of ethanol sensitivity are not well correlated [29]. Effects by TAGs in a SLO-1-dependent manner and general neuronal excitability effects are not mutually exclusive models, and in fact these two postulated lipid effects may act in concert to modify ethanol response at the behavioral level.
