Bead-like passage of chloride ions through ClC chloride channels Original Research Article

The ClC chloride channels control the ionic composition of the cytoplasm and the volume of cells, and regulate electrical excitability. Recently, it has been proposed that prokaryotic ClC channels are H+–Cl− exchange transporter. Although X-ray and molecular dynamics (MD) studies of bacterial ClC channels have investigated the filter open–close and ion permeation mechanism of channels, details have remained unclear. We performed MD simulations of ClC channels involving H+, Na+, K+, or H3O+ in the intracellular region to elucidate the open–close mechanism, and to clarify the role of H+ ion an H+–Cl− exchange transporter. Our simulations revealed that H+ and Na+ caused channel opening and the passage of Cl− ions. Na+ induced a bead-like string of Cl−–Na+–Cl−–Na+–Cl− ions to form and permeate through ClC channels to the intracellular side with the widening of the channel pathway.