Principles of single-channel kinetic analysis.

Single-channel recording provides high resolution information on gating mechanisms of ion channels that are generally difficult to obtain from macroscopic measurements. Analysis of the data, however, has proven to be challenging. Early approaches rely on half-amplitude threshold detection to idealize the record into dwell-times, followed by fitting duration histograms to resolve kinetics. More recent analyses exploit explicit modeling of the data to improve the idealization accuracy. The dwell-time fitting has also evolved into direct fitting of dwell-time sequences using the maximum likelihood approach while taking account of effects of missed events. Finally, hidden Markov modeling provides an ultimate approach by which both single channel amplitudes and kinetics are analyzed simultaneously without the need of idealization. The progress in theory, along with the advance in computing power as well as the development of user-friendly software, has transformed single-channel analysis, once a specialty task, now readily accessible to a broader community of scientists.