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Summary: Loose Protein Packing around the Extracellular Half of the GABAA
Receptor 1 Subunit M2 Channel-lining Segment*
Received for publication, December 22, 2003, and in revised form, January 6, 2004
Published, JBC Papers in Press, January 8, 2004, DOI 10.1074/jbc.M314050200
Eric N. Goren, David C. Reeves, and Myles H. Akabas
From the Departments of Physiology and Biophysics and of Neuroscience, Albert Einstein College of Medicine
of Yeshiva University, Bronx, New York 10461
GABAA receptors are ligand-gated ion channels
formed by the pseudosymmetrical assembly of five ho-
mologous subunits around the central channel axis.
The five M2 membrane-spanning segments largely line
the channel. In the present work we probed the water
surface accessibility of the 1 subunit M2 segment us-
ing the substituted cysteine accessibility method. We
assayed the reaction of the negatively charged sulfhy-
dryl-specific reagent, p-chloromercuribenzenesulfonate
(pCMBS ), by its effect on subsequent currents elicited
by EC50 and saturating GABA concentrations. pCMBS ,
applied with GABA, reacted with 14 of the 19 residues
tested. At the M2 cytoplasmic end from 2 to 6 only
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