Barrier-less knock-on conduction in ion channels: peculiarity or general mechanism?

A mechanism of barrier-less knock-on conduction is postulated for the best-studied KcsA ion channel. The conduction proceeds as follows: an ion enters the channel, which already contains two ions and "push" them along the pore. As a result, the state of triple occupancy forms. Eventually, the ion from the opposite side escapes to solution and the state of double occupancy is restored. The energies of the states with double and triple occupancies are almost the same, which makes alternation of these states possible. However, it is not known whether this mechanism is universal or specific for a narrow class of KcsA-like channels, which can accommodate just two or three ions in the selectivity filter. In the present work we develop a simplified model of the ion channel selectivity filter, which allows us to study the conduction in a broad range of ion occupancies using the Brownian dynamics. We show that knock-on barrier-less conduction occurs when the energies of adjacent equilibrium occupancy states are the same, regardless of the exact number of ions accommodated in the channel. It is shown that the maximal possible current flows through the channel in the regime of knock-on conduction. This allows us to conclude that knock-on barrier-less conduction can be considered as a universal mechanism of ions' translocation in the ion channels with multiple occupancy. (c) 2004 Elsevier B.V. All rights reserved.