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PMID: 1385113 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The atypical M2 segment of the beta subunit confers picrotoxinin resistance to inhibitory glycine receptor channels.

The EMBO journal ·Vol. 11 ·No. 12 ·1992-12-00 ·Pages 4305-11

Pribilla I, Takagi T, Langosch D, Bormann J, Betz H

Abstract

Purified preparations of the inhibitory glycine receptor (GlyR) contain alpha and beta subunits, which share homologous primary structures and a common transmembrane topology with other members of the ligand-gated ion channel superfamily. Here, a beta subunit-specific antiserum was shown to precipitate the [3H]strychnine binding sites localized on alpha subunits from membrane extracts of both rat spinal cord and mammalian cells co-transfected with alpha and beta cDNAs. Further, inhibition of alpha homo-oligomeric GlyRs by picrotoxinin, a non-competitive blocker of ion flow, was reduced 50- to 200-fold for alpha/beta hetero-oligomeric receptors generated by cotransfection. Site-directed mutagenesis identified residues within the second predicted transmembrane segment (M2) of the beta subunit as major determinants of picrotoxinin resistance. These data implicate the M2 segment in blocker binding to and lining of the GlyR chloride channel.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cell Line Cells, Cultured Cerebellum/metabolism Cloning, Molecular DNA Glycine/metabolism Humans Ion Channels/drug effects,genetics Molecular Sequence Data Mutagenesis, Site-Directed Picrotoxin/analogs & derivatives,pharmacology Rats Receptors, Glycine Receptors, Neurotransmitter/drug effects,genetics,metabolism Sequence Homology, Amino Acid Sesterterpenes Spinal Cord/metabolism Strychnine/metabolism
Chemicals
Ion Channels Receptors, Glycine Receptors, Neurotransmitter Sesterterpenes Picrotoxin DNA picrotoxinin Strychnine Glycine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pribilla I
Zentrum für Molekulare Biologie, Universität Heidelberg, Germany.
Takagi T
Langosch D
Bormann J
Betz H
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1992-12-00
Pages
4305-11
Language
English
Region
England
NLM ID
8208664
PMCID
PMC557003
Subset
IM
Corrections
ErratumIn
PMID: 8137831
External Links
PubMed source PMC Full Text View journal details
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