Whereas the previous section describes a mechanism of tolerance related to isoform variability in the α subunit of the BK channel, in this section we will describe the influence of the BK auxiliary β subunits on tolerance. The BK channel, which is mainly understood to act as a ‘brake’ on neural activity [21,78,79] (although excitatory effects have also been reported [20]), is composed of a primary α protein, containing a pore that acts as a conduit for potassium ions, often combined with a variety of auxiliary proteins (β1–β4) that modify its function, including alcohol sensitivity (Box 1). Compartment-specific expression of β subunits of the BK channel has been proposed to underlie differences in BK alcohol sensitivity between the somatic, dendritic and terminal compartments of neurons [9]. One of these auxiliary proteins, known as β4, plays a key role in acute alcohol tolerance. Importantly, one of the most reliable predictors of future alcohol problems in humans is the presence of an enhanced ability to develop acute tolerance in a cognitive task (i.e. performance recovers in spite of the continued presence of a constant blood–alcohol level).
