The response of BK activity to acute alcohol challenge varied among isoforms (Figure 6A). The presence of the ALCOREX exon produced BK channels with the greatest alcohol sensitivity of those tested: the magnitude of potentiation was largest, and persisted the longest (Figure 6B). INSERTLESS BK channels were also potentiated by alcohol, but to a much smaller degree than ALCOREX and returned to baseline faster (Figure 6A, B). In contrast, the mRNA variant encoding a BK channel with STREX produced channels which were resistant to alcohol (Figure 6B). Measurements made in cell-attached mode at lower Ca2+ levels, designed to provide optimal opportunity for alcohol to potentiate gating by lowering NPo, confirmed the absence of alcohol potentiation in STREX channels (data not shown). Integrated measurement of the magnitude and the duration of alcohol potentiation (area under the curve in Figure 6B, see Methodology), which corresponds to ion flow through the channel, show the differences in acute alcohol sensitivity of BK variants (Figure 6C).
