The βM3-4’residue was further demonstrated to be part of the binding site for the intravenous anesthetic propofol (Bali & Akabas, 2004) and to be affinity labeled with an analogue of etomidate (Li et al., 2006), which also identified a second residue in αM1 (11’). Residues αM1 (11’) and βM3-4’were proposed to contribute to a single intersubunit binding pocket at the β/α subunit interface, 50 Ǻ below the GABA binding pocket in the extracellular domain (Li et al., 2006). The residues in αM1 and βM3 were shown to be facing each other by cross-linking of helical cysteine-substituted residues (Jansen & Akabas, 2006; Bali et al., 2007) supporting the conclusion that residues αM1-11’ and βM3-4’ are likely to be positioned appropriately to participate in an intersubunit pocket. This conclusion is also consistent with homology modeling using the Unwin (2005) structure of the nAChR as a template. Further experiments will have to clarify whether βM3-4’contributes to an intrahelical or interhelical pocket.
