The properties of the human a1b1 g-aminobutyric acid (GABA)A receptors were investigated after mutation of a highly conserved leucine residue at the 99 position in the second membrane-spanning region (TM2). The role of this residue in a1 and b1 subunits was examined by mutating the 99 leucine to phenylalanine, tyrosine, or alanine. The mutations were in either the a1 subunit (apb), the b1 subun...