In the final step, we calculated the overall responsiveness to alcohol of the composite BK channel population (Eq. 2, Methodology) as a measure of alcohol tolerance. Since we did not know the level of ALCOREX/INSERTLESS heteromer potentiation by alcohol (category # 4), we ran the model through two extreme variations: alcohol potentiation of the ALCOREX/INSERTLESS heteromer is 1) as low as the INSERTLESS homomer, or 2) as high as the ALCOREX homomer. These two extremes provided upper and lower limits of the possible level of ALCOREX/INSERTLESS potentiation by alcohol, and allowed us to determine the potential range of the decrease in total alcohol responsiveness of the BK channel in neurons. Clearly, even in the most conservative calculation (variation # 1) a 15–30 min exposure to alcohol resulted in BK channels with only 15 % of naive neuron responsiveness, exhibiting almost complete tolerance to alcohol (an even more profound effect was evident in variation # 2, not shown), in both SON and striatal neurons (Figure 7D). Moreover, longer alcohol exposures caused an augmentation of alcohol tolerance (Figure 7D, 6 hrs, 24 hrs).
