Residues lining the inner pore vestibule of human muscle chloride channels

Christoph Fahlke*, Reshma R. Desai, Niloufar Gillani, Alfred L. George

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Chloride channels belonging to the C1C family are ubiquitous and participate in a wide variety of physiological and pathophysiological processes. To define sequence segments in C1C channels that contribute to the formation of their ion conduction pathway, we employed a combination of site-directed mutagenesis, heterologous expression, patch clamp recordings, and chemical modification of the human muscle C1C isoform, hC1C-1. We demonstrate that a highly conserved 8-amino acid motif (P3) located in the linker between transmembrane domains D2 and D3 contributes to the formation of a wide pore vestibule facing the cell interior. Similar to a previously defined pore region (P1 region), this segment functionally interacts with the corresponding segment of the contralateral subunit. The use of cysteine-specific reagents of different size revealed marked differences in the diameter of pore-forming regions implying that C1C channels exhibit a pore architecture quite similar to that of certain cation channels, in which a narrow constriction containing major structural determinants of ion selectivity is neighbored by wide vestibules on both sides of the membrane.

Original languageEnglish (US)
Pages (from-to)1759-1765
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number3
DOIs
StatePublished - Jan 19 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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