PubMed 11035024

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC1 , ClvC4 , Kv10.1

Title: Residues lining the inner pore vestibule of human muscle chloride channels.

Authors: C Fahlke, R R Desai, N Gillani, A L George

Journal, date & volume: J. Biol. Chem., 2001 Jan 19 , 276, 1759-65

PubMed link:

Chloride channels belonging to the ClC family are ubiquitous and participate in a wide variety of physiological and pathophysiological processes. To define sequence segments in ClC 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 ClC isoform, hClC-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 ClC 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.