A threonine residue in the M2 region of the beta(1) subunit is needed for expression of functional alpha(1)beta(1) GABA(A) receptors

Although then is a high degree of homology in the M2 transmembrane segments of alpha(1) and beta(1) subunits, subunit-specific effects were observed i n alpha(1)beta(1) GABA(A) receptors expressed in Spodoptera frugipedra (Sf9 ) cells when the conserved 13' threonine residue in the M2 transmembrane re gion was mutated to alanine. When threonine 263 (13') was mutated to alanin e in the beta(1) subunit, high-affinity muscimol binding and the response t o GABA were abolished. This did not occur when the threonine 263 (13') was mutated to alanine in the alpha(1) subunit, but the rate of desensitisation increased and the effect of bicuculline, a competitive inhibitor, was redu ced. The results show differential effects of subunits on receptor function and support a role for M2 in desensitisation. (C) 1999 Elsevier Science B. V. All rights reserved.