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Interaction of picrotoxin with GABAA receptor channel-lining residues probed in cysteine mutants.
Xu M
,
Covey DF
,
Akabas MH
.
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We used the substituted-cysteine-accessibility method to identify the channel-lining residues in a region (257-261) near the putative cytoplasmic end of the M2 membrane-spanning segment of the rat gamma-aminobutyric acid type A (GABAA) receptor alpha 1 subunit. The residues alpha 1Val257 and alpha 1Thr261 were accessible to charged, sulfhydryl-specific reagents applied extracellularly in both the open and closed states. The accessibility of alpha 1V257C and alpha 1T261C in the closed state implies that the gate must be at least as close to the cytoplasmic end of the channel as alpha 1Val257. Also, the positively charged reagent methanethiosulfonate ethylammonium penetrated from the extracellular end of the channel to alpha 1T261C, with which it reacted, indicating that the anion-selectivity filter is closer to the cytoplasmic end of the channel than this residue is. Co-application of picrotoxin prevented the sulfhydryl reagents from reacting with alpha 1V257C but did not prevent reaction with the more extracellular residue alpha 1T261C. Picrotoxin protection of alpha 1V257C may be due to steric block by picrotoxin bound in the channel at the level of alpha 1Val257; however, if this protection is allosteric, it is not due to the induction of the resting closed state in which alpha 1V257C was accessible to sulfhydryl reagent.
Akabas,
Acetylcholine receptor channel structure probed in cysteine-substitution mutants.
1992,
Pubmed
,
Xenbase
Akabas,
Identification of acetylcholine receptor channel-lining residues in the entire M2 segment of the alpha subunit.
1994,
Pubmed
,
Xenbase
Amin,
GABAA receptor needs two homologous domains of the beta-subunit for activation by GABA but not by pentobarbital.
1993,
Pubmed
,
Xenbase
Bormann,
Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones.
1987,
Pubmed
Canney,
Synthesis and structure-activity studies of alkyl-substituted gamma-butyrolactones and gamma-thiobutyrolactones: ligands for the picrotoxin receptor.
1991,
Pubmed
Cohen,
Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations.
1992,
Pubmed
,
Xenbase
Cully,
Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans.
1994,
Pubmed
,
Xenbase
ffrench-Constant,
A single-amino acid substitution in a gamma-aminobutyric acid subtype A receptor locus is associated with cyclodiene insecticide resistance in Drosophila populations.
1993,
Pubmed
Ffrench-Constant,
A point mutation in a Drosophila GABA receptor confers insecticide resistance.
1993,
Pubmed
,
Xenbase
Galzi,
Mutations in the channel domain of a neuronal nicotinic receptor convert ion selectivity from cationic to anionic.
1992,
Pubmed
,
Xenbase
Gurley,
Point mutations in the M2 region of the alpha, beta, or gamma subunit of the GABAA channel that abolish block by picrotoxin.
1995,
Pubmed
,
Xenbase
Holland,
Gamma-butyrolactone antagonism of the picrotoxin receptor: comparison of a pure antagonist and a mixed antagonist/inverse agonist.
1991,
Pubmed
Imoto,
Rings of negatively charged amino acids determine the acetylcholine receptor channel conductance.
1988,
Pubmed
,
Xenbase
Inoue,
Blockade of gamma-aminobutyric acid-gated chloride current in frog sensory neurons by picrotoxin.
1988,
Pubmed
Karlin,
Structure of nicotinic acetylcholine receptors.
1993,
Pubmed
Khrestchatisky,
A novel alpha subunit in rat brain GABAA receptors.
1989,
Pubmed
,
Xenbase
Macdonald,
GABAA receptor channels.
1994,
Pubmed
Maconochie,
How quickly can GABAA receptors open?
1994,
Pubmed
Maksay,
Dissociation of [35S]t-butylbicyclophosphorothionate binding differentiates convulsant and depressant drugs that modulate GABAergic transmission.
1985,
Pubmed
Nagata,
Selective effects of dieldrin on the GABAA receptor-channel subunits expressed in human embryonic kidney cells.
1994,
Pubmed
Newland,
On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.
1992,
Pubmed
Olsen,
Molecular biology of GABAA receptors.
1990,
Pubmed
Porter,
Kinetic properties of alpha 1 beta 1 gamma-aminobutyric acidA receptor channels expressed in Chinese hamster ovary cells: regulation by pentobarbital and picrotoxin.
1992,
Pubmed
Pribilla,
The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels.
1992,
Pubmed
Schofield,
Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family.
,
Pubmed
,
Xenbase
Shivers,
Two novel GABAA receptor subunits exist in distinct neuronal subpopulations.
1989,
Pubmed
Squires,
[35S]t-butylbicyclophosphorothionate binds with high affinity to brain-specific sites coupled to gamma-aminobutyric acid-A and ion recognition sites.
1983,
Pubmed
Stauffer,
Electrostatic potential of the acetylcholine binding sites in the nicotinic receptor probed by reactions of binding-site cysteines with charged methanethiosulfonates.
1994,
Pubmed
Ticku,
Binding of [3H]alpha-dihydropicrotoxinin, a gamma-aminobutyric acid synaptic antagonist, to rat brain membranes.
1978,
Pubmed
Twyman,
Pentobarbital and picrotoxin have reciprocal actions on single GABAA receptor channels.
1989,
Pubmed
Twyman,
Kinetics of open channel block by penicillin of single GABAA receptor channels from mouse spinal cord neurones in culture.
1992,
Pubmed
Unwin,
Acetylcholine receptor channel imaged in the open state.
1995,
Pubmed
Unwin,
Nicotinic acetylcholine receptor at 9 A resolution.
1993,
Pubmed
VANSTEVENINCK,
LOCALIZATION OF ERYTHROCYTE MEMBRANE SULFHYDRYL GROUPS ESSENTIAL FOR GLUCOSE TRANSPORT.
1965,
Pubmed
Villarroel,
Location of a threonine residue in the alpha-subunit M2 transmembrane segment that determines the ion flow through the acetylcholine receptor channel.
1991,
Pubmed
,
Xenbase
Wisden,
GABAA receptor channels: from subunits to functional entities.
1992,
Pubmed
Xu,
Amino acids lining the channel of the gamma-aminobutyric acid type A receptor identified by cysteine substitution.
1993,
Pubmed
,
Xenbase
Yan,
Identification of a residue in the translocation pathway of a membrane carrier.
1993,
Pubmed
Ymer,
GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs.
1989,
Pubmed
,
Xenbase
Yoon,
Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons.
1993,
Pubmed
Zhang,
A unique amino acid of the Drosophila GABA receptor with influence on drug sensitivity by two mechanisms.
1994,
Pubmed
