The role of conformational diffusion in ion channel gating

We consider an exactly tractable model of the Kramers type for the voltage-dependent gating dynamics of single ion channels. It is assumed that the gating dynamics is caused by the thermally activated transitions in a bistable potential. Moreover, the closed state of the channel is highly degenerate and embraces the whole manifold of closed substates. Opening of the ion channel is energetically prohibited from most of the closed substates and requires a special conformation where the voltage sensor can move along an activation pathway and trigger the transition into the open conformation. When the corresponding activation barrier towards the channel's opening is removed by the applied voltage, the statistics of non-conducting time intervals become strongly influenced by the conformational diffusion. For the corresponding supra-threshold voltages, our model explains the origin of the power law distribution of the closed time intervals. The exponential-linear dependence of the opening rate on voltage, often used as an experimental fit, is also reproduced by our model. (C) 2003 Elsevier Science B.V. All rights reserved.