Furthermore, alternative mechanisms through which alcohol could exert its effects were possible, such as increasing the fluidity of the plasma membrane20, 21. Another example of a putative G protein-independent modulator is cholesterol. Cholesterol, which accounts for up to 50% of the total lipid membrane content22, has been shown to modulate the activity of potassium channels23–28, including cardiac GIRK channels, i.e., GIRK1/GIRK4 subunits23, 27. However, whether cholesterol affects brain GIRK channels, comprised mostly of GIRK2-containing tetramers, requires Gβγ subunits, and interacts with alcohol-dependent activation is unknown1.
