Here, we have presented data from several approaches that probe the response of the BK channel to ethanol, indicating that the response is more specific and interpretable than textbook doctrine would have suggested for alcohol–protein interactions just 20 years ago. The data described raise many interesting questions. Why are there so many different mechanisms to produce and modify BK alcohol tolerance? Clearly, the neuron finds it important to minimize the consequences of the influence of alcohol on BK activity. This is understandable by virtue of the very high conductance and ubiquity of the BK channel within and outside the nervous system, such that altered activity could have devastating outcomes on function. Thus, not only is the channel quickly desensitized to ethanol potentiation but then a ‘sledgehammer’ approach is apparent in the subsequent internalization of BK, removing it from the functional influence of alcohol. A testable assumption is that different drinking patterns will elicit different varieties of tolerance. For example, characteristics of tolerance produced by drinking that is ‘massed’ (i.e. long drinking bouts) versus ‘spaced’ (i.e. shorter, intermittent bouts of drinking)
