2011b). Alcohol has been reported to affect several ion channels in the brain. For example, ethanol modulates GABAA (Mihic et al., 1994) glycine receptors (Mihic et al., 1997), Ca2+-dependent K+ channels (Dopico et al., 1998), and acetylcholine receptors (Cardoso et al., 1999), while ethanol inhibits NMDA receptors (Lovinger et al., 1989). In spite of widely documented effects of alcohol on ion channels and receptors, the demonstration of a direct interaction with an ion channel has been elusive. Unlike canonical ligands that saturate a physical binding site, it has been difficult to show saturation of the alcohol binding pocket because the modulatory effects of ethanol occur in the milliMolar range; saturation would not be evident until ethanol reaches hundreds of milliMolar (>300 mM).
