CHARACTERIZATION OF SINGLE CHANNEL CURRENTS USING DIGITAL SIGNAL-PROCESSING TECHNIQUES BASED ON HIDDEN MARKOV-MODELS

Techniques for extracting small, single channel ion currents from background noise are described and tested. It is assumed that single channel currents are generated by a first-order, finite-state, discrete-time, Markov process to which is added 'white' background noise from the recording apparatus (electrode, amplifiers, etc). Given the observations and the statistics of the background noise, the techniques described here yield a posteriori estimates of the most likely signal statistics, including the Markov model state transition probabilities, duration (open- and closed-time) probabilities, histograms, signal levels, and the most likely state sequence. Using variations of several algorithms previously developed for solving digital estimation problems, we have demonstrated that: (1) artificial, small, first-order, finite-state, Markov model signals embedded in simulated noise can be extracted with a high degree of accuracy, (2) processing can detect signals that do not conform to a first-order Markov model but the method is less accurate when the background noise is not white, and (3) the techniques can be used to extract from the baseline noise single channel currents in neuronal membranes. Some studies have been included to test the validity of assuming a first-order Markov model for biological signals. This method can be used to obtain directly from digitized data, channel characteristics such as amplitude distributions, transition matrices and open- and closed-time durations.