After determining the tetrameric make up of BK channels in neurons, we considered alcohol sensitivity of various assemblies. In Figure 6C we described different alcohol effects on different BK homomers (potentiation of INSERTLESS and ALCOREX by alcohol vs STREX alcohol resistance). Interestingly, recent reports (Tian et al. 2001, Tian et al., 2004) described a similar differential effect, with respect to the action of PKA phosphorylation on BK homomer activity: i.e. INSERTLESS potentiation and STREX inhibition. Moreover, the STREX channel was inhibited even when only a single STREX monomer was present within a heteromer. We reasoned that if STREX alcohol resistance was mediated by PKA, then similar dominance of the STREX insert (i.e. alcohol resistance) within heteromers might occur. Using a specific PKA inhibitor (14–22 Amide) we found that the alcohol resistance of STREX is indeed PKA-dependent (Figure 7C). Thus, we assumed that any BK channel containing a STREX monomer is alcohol resistant to the same degree as a STREX homomer.
