Fig. 2. Alignment of human nicotinic α7 and mouse 5-hydroxytryptamine-3A (5HT^3A) protein sequence in the predicted transmembrane segment 2 region and the extracellular loop between transmembrane segments 2 and 3. (A ) Common amino acid residues are indicated in light text , and those that differ are indicated in bold text . For each amino acid residue that differed in the sequence alignment above, a mutant nicotinic α7 subunit was constructed such that a single amino acid residue occurs in the native 5HT^3Asubunit. (B ) Percentage of current remaining when the wild-type nicotinic α7 and 22 mutant nicotinic α7 receptors are inhibited by 20 μm ketamine. The wild-type α7 nicotinic receptor was inhibited 61 ± 3%. Of the 22 mutant α7 subunits constructed, 18 formed activating homomeric nicotinic receptors in oocytes. Only a single mutant, A258S, resulted in a receptor that was significantly resistant to inhibition by ketamine. The A258S α7 nicotinic mutant was inhibited 35 ± 1% by 20 μm ketamine (t  test; P < 0.001). Number of oocytes for each data point = 5–12. Values are expressed as mean ± SE.