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TheJournalofGeneralPhysiology J. Gen. Physiol. The Rockefeller University Press $15.00
 

Summary: TheJournalofGeneralPhysiology
J. Gen. Physiol. The Rockefeller University Press $15.00
Volume 129 Number 2 February 2007 145159
http://www.jgp.org/cgi/doi/10.1085/jgp.200609639
145
A RT I C L E
The Location of a Closed Channel Gate in the GABAA
Receptor Channel
Moez Bali and Myles H. Akabas
Departments of Physiology and Biophysics, Neuroscience, and Medicine, Albert Einstein College of Medicine of Yeshiva
University, Bronx, NY 10461
Considerable controversy surrounds the location of the closed channel gate in members of the Cys-loop receptor
family of neurotransmitter-gated ion channels that includes the GABAA, glycine, acetylcholine, and 5-HT3 recep-
tors. Cysteine-accessibility studies concluded that the gate is near the cytoplasmic end of the channel in acetylcho-
line and GABAA receptors but in the middle of the 5-HT3A receptor channel. Zn2+ accessibility studies in a chimeric
5-HT3-ACh receptor suggested the gate is near the channel's cytoplasmic end. In the 4- resolution structure of the
acetylcholine receptor closed state determined by cryoelectron microscopy, the narrowest region, inferred to be
the gate, is in the channel's midsection from 9' to 14' but the M1M2 loop residues at the channel's cytoplasmic
end were not resolved in that structure. We used blocker trapping experiments with picrotoxin, a GABAA receptor
open channel blocker, to determine whether a gate exists at a position more extracellular than the picrotoxin bind-

  

Source: Akabas, Myles - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Yeshiva University

 

Collections: Biology and Medicine