To determine how these changes in various transcripts might contribute to alcohol tolerance we developed a computational model integrating our molecular biological and electrophysiological outcomes. Importantly, BK channels can function only as tetrameric assemblies of four monomers, where each monomer is encoded by individual BK transcript. To assess the functional consequences of alcohol regulation of BK transcripts, we incorporated into the model published data describing differential effects of PKA on different BK tetramers (Tian et al., 2004), and our new data describing the relative functional weighting of monomers in determining alcohol sensitivity of assembled BK channel tetramers.
