| | |
Summary: -Aminobutyric Acid Increases the Water Accessibility of M3 Membrane-
Spanning Segment Residues in -Aminobutyric Acid Type A Receptors
Daniel B. Williams*#
and Myles H. Akabas*§
*Center for Molecular Recognition, #
Integrated Program in Cellular, Molecular, and Biophysical Studies, and §
Department of Physiology
and Cellular Biophysics and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York,
New York 10032 USA
ABSTRACT -Aminobutyric acid type A (GABAA) receptors are members of the ligand-gated ion channel gene superfamily.
Using the substituted cysteine accessibility method, we investigated whether residues in the 1M3 membrane-spanning
segment are water-accessible. Cysteine was substituted, one at a time, for each M3 residue from 1Ala291
to 1Val307
. The
ability of these mutants to react with the water-soluble, sulfhydryl-specific reagent pCMBS was assayed electrophysiologi-
cally. Cysteines substituted for 1Ala291
and 1Tyr294
reacted with pCMBS applied both in the presence and in the absence
of GABA. Cysteines substituted for 1Phe298
, 1Ala300
|
