Correcting single channel data for missed events

Abstract

Interpretation of currents recorded from single ion channels in cellular membranes or lipid bilayers is complicated by the necessarily limited time resolution of the recording and detection systems. All intervals less than a certain duration, depending on the frequency response of the system, are not detected. Such missed events produce increases in the durations of observed open and shut intervals. In order to obtain the true kinetic scheme and rate constants underlying the observed activity, it is necessary to take into account missed events. We develop methods to correct for missed events for models with two or more states, including models with multiple open and shut states, compound states, and loops. Our methods can be used in a forward direction to predict observed distributions of open and shut intervals for a given kinetic scheme and time resolution. They can also be used in a backwards direction with iterative methods to determine rate constants consistent with the observed distributions. While a given kinetic scheme with rate constants predicts unique observed distributions of open and shut intervals, rate constants determined from observed distributions are not necessarily unique. Using these correction methods, we examine the effects of missed events for a five-state model consistent with some properties of large conductance Ca-activated K channels.