Locations where Arg substitution regulates fatty acid inhibition and potentiation. Homology model of the transmembrane portions of GluK2(Q) based on the x-ray crystal structure of GluA2. (A) View down the central axis of the pore from outside the cell. (B) Same orientation as A, but with the a, b and c, d subunit pairs separated by lateral displacement. (C) Side view of the subunit pairs in B, after 90° rotation, illustrating residues that face the pore (left) or surrounding lipids (right). Locations where Arg substitution promoted strong or intermediate inhibition by DHA are colored red and yellow, respectively. Green indicates positions where Arg substitution did not alter susceptibility of GluK2(Q) to DHA. Little or no whole-cell current was elicited from subunits with Arg substituted a locations colored black. Blue indicates the three Arg substitution positions in M3 where exposure to DHA resulted in potentiation of whole-cell currents. Residues colored gray were not substituted in this study. M4 helices are semi-transparent, for clarity.