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

Iris Pribilla, Tamaki Takagi, Dieter Langosch, Joachim Bormann, Heinrich Betz

Research output: Contribution to journalArticlepeer-review

323 Scopus citations

Abstract

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

Original languageEnglish
Pages (from-to)4305-4311
Number of pages7
JournalEMBO Journal
Volume11
Issue number12
StatePublished - 1992
Externally publishedYes

Keywords

  • Channel block
  • Glycine receptor
  • Heterologous expression
  • Picrotoxinin
  • Subunit assembly

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