A critical tool in the understanding of the role of the β subunit in tolerance and consumption has been the use of genetically engineered mice, in which the gene encoding the β4 subunit is ‘knocked out’ (KO). The KO mouse allows analysis of tolerance at multiple levels, from single channel recording of the individual BK channel protein through to cellular analysis at the level of the action potential and ultimately to drinking behavior [3]. There is remarkable consistency in the results showing that the β4 subunit inhibits acute tolerance at all levels of analysis and confirming that, in the mouse model, the presence of acute tolerance is an indicator of alcohol consumption, as has been described in human studies (Figure 4). At the single-channel level, ab4 BK channels from the somata of wild type (WT) striatal medium spiny neurons (a crucial element of the reward and addiction pathway) are potentiated by alcohol, and this potentiation shows no tolerance throughout the recording session (Figure 4b, αβ4 BK). By contrast, when the β4 auxiliary subunit is absent, alcohol-mediated potentiation of BK channel
