Barttin activates ClC-K channel function by modulating gating.
Barttin is an accessory subunit that modifies protein stability, subcellular distribution, and voltage-dependent gating of ClC-K chloride channels expressed in renal and inner ear epithelia. ClC-K channels are double-barreled channels with two identical protopores that may be opened by individual or common gating processes. Using heterologous expression in mammalian cells and patch-clamp recordings, we studied the effects of barttin on gating of rat ClC-K1 and human ClC-Ka. In the absence of barttin, rClC-K1 channels displayed two gating processes with distinct kinetics and voltage dependence. A fast gating process, activated by membrane hyperpolarization, opens and closes individual rClC-K1 protopores. In addition, slow common gating steps, stimulated by membrane depolarization, act on both protopores together. Coexpression of barttin results in voltage-independent open probabilities of the common gate, causing increased channel activity at physiologic potentials. In contrast to rClC-K1, human ClC-Ka is functional only when coexpressed with barttin. Single-channel recordings of hClC-Ka/barttin show double-barreled channels with fast protopore gating without apparent cooperative gating steps. These findings demonstrate that barttin stimulates chloride flux through ClC-K channels by modifying cooperative gating of the double-barreled channels and highlight a physiologic role for gating of epithelial ClC chloride channels.
Institut für Neurophysiologie, Medizinische Hochschule Hannover, Hannover, Germany.
Martin
M
Fischer
Audrey G H
AG
Janssen
Christoph
C
Fahlke
D000818:Animals; D018118:Chloride Channels / Q000502:physiology*; D055724:Electrophysiological Phenomena; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D021122:Protein Subunits / Q000502:physiology*; D051381:Rats
C440005:BSND protein, human; C412733:CLCNKB protein, human; D018118:Chloride Channels; D021122:Protein Subunits