We show here also that INSERTLESS and ALCOREX exhibit different patterns of alcohol sensitivity and channel density. The molecular mechanisms underlying these differences are, at this point, unclear. These two BK isoforms do not have apparent differences in consensus phosphorylation sequence (NetPhos 2.0, data not shown), making this an unlikely explanation for the difference in short-term adaptation. Possibly, the insertion of ALCOREX produces a conformational change in the BK polypeptide, resulting in a change in potentiation by alcohol. The ALCOREX insert is located just 10 residues upstream of the calcium bowl, and this physical proximity could potentially change the interaction of the calcium bowl with calcium ions and subsequently affect channel activity. Indeed, as reported by Ha (Ha et al., 2000) the BK channel with an insert encoded by exon 29 (rSlo27 = ALCOREX) activates faster than BK channels without this insert, dependent upon calcium concentration. Previous data (Dopico et al., 1998) indicate that alcohol acts as a partial agonist of the BK channel, with calcium as full agonist. Another intriguing possibility derives from recent work, which has shown that
