PubMed 18801843

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC2 , ClvC4 , Slo1

Title: Gating of human ClC-2 chloride channels and regulation by carboxy-terminal domains.

Authors: Jennie Garcia-Olivares, Alexi Alekov, Mohammad Reza Boroumand, Birgit Begemann, Patricia Hidalgo, Christoph Fahlke

Journal, date & volume: J. Physiol. (Lond.), 2008 Nov 15 , 586, 5325-36

PubMed link:

Eukaryotic ClC channels are dimeric proteins with each subunit forming an individual protopore. Single protopores are gated by a fast gate, whereas the slow gate is assumed to control both protopores through a cooperative movement of the two carboxy-terminal domains. We here study the role of the carboxy-terminal domain in modulating fast and slow gating of human ClC-2 channels, a ubiquitously expressed ClC-type chloride channel involved in transepithelial solute transport and in neuronal chloride homeostasis. Partial truncation of the carboxy-terminus abolishes function of ClC-2 by locking the channel in a closed position. However, unlike other isoforms, its complete removal preserves function of ClC-2. ClC-2 channels without the carboxy-terminus exhibit fast and slow gates that activate and deactivate significantly faster than in WT channels. In contrast to the prevalent view, a single carboxy-terminus suffices for normal slow gating, whereas both domains regulate fast gating of individual protopores. Our findings demonstrate that the carboxy-terminus is not strictly required for slow gating and that the cooperative gating resides in other regions of the channel protein. ClC-2 is expressed in neurons and believed to open at negative potentials and increased internal chloride concentrations after intense synaptic activity. We propose that the function of the ClC-2 carboxy-terminus is to slow down the time course of channel activation in order to stabilize neuronal excitability.