intersubunit crevice close to the transmembrane domain (M2), which undergoes a conformational rotation during channel activation (Sauguet et al., 2013). Thus, in both channels, alcohol may serve as an allosteric modulator. Lastly, the chemical interactions of alcohol in the pocket involve both hydrophobic and hydrophilic residues. One notable difference is the physical location of the alcohol pocket. In GLIC, the alcohol pocket is located in the transmembrane domains while the pocket in GIRK channels is situated within the cytoplasmic domains. We anticipate that high resolution structures of alcohol in complex different conformational states of the channel in the future will further clarify the molecular mechanism underlying alcohol modulation of ion channels.
