The Power of Two-Dimensional Dwell-Time Analysis for Model Discrimination, Temporal Resolution, Multichannel Analysis and Level Detection |
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Authors: | Tobias Huth Indra Schroeder Ulf-Peter Hansen |
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Institution: | (1) Department of Physiology, University of Kiel, Olshausenstrasse 40, D-24098 Kiel, Germany;(2) Center of Biochemistry and Molecular Biology, University of Kiel, Leibnizstrasse 11, D-24098 Kiel, Germany |
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Abstract: | Two-dimensional (2D) dwell-time analysis of time series of single-channel patch-clamp current was improved by employing a
Hinkley detector for jump detection, introducing a genetic fit algorithm, replacing maximum likelihood by a least square criterion,
averaging over a field of 9 or 25 bins in the 2D plane and normalizing per measuring time, not per events. Using simulated
time series for the generation of the “theoretical” 2D histograms from assumed Markov models enabled the incorporation of
the measured filter response and noise. The effects of these improvements were tested with respect to the temporal resolution,
accuracy of the determination of the rate constants of the Markov model, sensitivity to noise and requirement of open time
and length of the time series. The 2D fit was better than the classical hidden Markov model (HMM) fit in all tested fields.
The temporal resolution of the two most efficient algorithms, the 2D fit and the subsequent HMM/beta fit, enabled the determination
of rate constants 10 times faster than the corner frequency of the low-pass filter. The 2D fit was much less sensitive to
noise. The requirement of computing time is a problem of the 2D fit (100 times that of the HMM fit) but can now be handled
by personal computers. The studies revealed a fringe benefit of 2D analysis: it can reveal the “true” single-channel current
when the filter has reduced the apparent current level by averaging over undetected fast gating. |
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Keywords: | Anti-aliasing filter Beta distribution Fast gating Genetic algorithm Hidden Markov model Ion channel Maximum likelihood Rate constant |
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