A cytoplasmic domain mutation in ClC-Kb affects long-distance communication across the membrane.

ABSTRACT:

Background

ClC-Kb and ClC-Ka are homologous chloride channels that facilitate chloride homeostasis in the kidney and inner ear. Disruption of ClC-Kb leads to Bartter's Syndrome, a kidney disease. A point mutation in ClC-Kb, R538P, linked to Bartter's Syndrome and located in the C-terminal cytoplasmic domain was hypothesized to alter electrophysiological properties due to its proximity to an important membrane-embedded helix.

Methodology/principal findings

Two-electrode voltage clamp experiments were used to examine the electrophysiological properties of the mutation R538P in both ClC-Kb and ClC-Ka. R538P selectively abolishes extracellular calcium activation of ClC-Kb but not ClC-Ka. In attempting to determine the reason for this specificity, we hypothesized that the ClC-Kb

SUBMITTER: Martinez GQ 

PROVIDER: S-EPMC2447174 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature