ncts

The CLC molecular family consists of two functionally defined subfamilies of membrane proteins catalyzing the transport of ions across plasma membranes: the CLC chloride channel subfamily and the CLC chloride-proton antiporter subfamily. CLC-0 (expressed in the Torpedo electric organ), CLC-1 (expressed in mammalian skeletal muscles) and CLC-2 (ubiquitously expressed in various mammalian cells) are chloride channels, in which the opening and closing (referred to as “gating”) of the channels have been thought to couple to the ion permeation through the pore. Although CLC-0 is not a mammalian channel, the functional properties of this Torpedo chloride channel are the best studied among all CLC molecules. CLC-0 is known to have two types of channel gating mechanisms: the fast gating and the slow gating (also called inactivation gating). The structural basis of the fast gating is thought to result from a competition of the permeant ion with the channel gate (the negatively charged glutamate sidechain) for a chloride-binding site in the pore. The structural basis of the slow gating, however, is still not understood. I will present some of our experiments and discuss how ion permeation in CLC channels controls the fast- and the slow-gating, and how chloride-proton transports across these molecules may be related to the gating of the channel.