Analysis of post-perturbation gating kinetics of single ion channels

Analysis of mean dwell-times as a function of the number of channel openings elapsed since a stepwise perturbation in ion-channel kinetics is shown to provide information concerning the topology of the underlying gating mechanism. The difference between the post-perturbation mean dwell-time and the corresponding equilibrium mean is shown to decay as the sum of Ng-1 geometric terms in k, the number of openings since the perturbation, where Ng is the minimum number of gateway states in the channel gating mechanism. The method is illustrated by consideration of various simple gating schemes. A modification of the method accommodating the presence of channel inactivation or desensitization is described. Application of the method to a delayed-rectifier type K+ channel of NG108-15 cells reveals that Ng greater than or equal to 2, consistent with a branched gating mechanism.