Hidden Markov analysis of mechanosensitive ion channel gating

Khan, R. Nazim, Martinac, Boris, Madsen, Barry W., Milne, Robin K., Yeo, Geoffrey F. and Edeson, Robert O. (2005) Hidden Markov analysis of mechanosensitive ion channel gating. Mathematical Biosciences, 193 2: 139-158. doi:10.1016/j.mbs.2004.07.007

Author Khan, R. Nazim
Martinac, Boris
Madsen, Barry W.
Milne, Robin K.
Yeo, Geoffrey F.
Edeson, Robert O.
Title Hidden Markov analysis of mechanosensitive ion channel gating
Journal name Mathematical Biosciences   Check publisher's open access policy
ISSN 0025-5564
Publication date 2005-02
Sub-type Article (original research)
DOI 10.1016/j.mbs.2004.07.007
Volume 193
Issue 2
Start page 139
End page 158
Total pages 20
Place of publication Philadelphia, PA, U.S.A.
Publisher Elsevier
Language eng
Abstract Patch clamp data from the large conductance mechanosensitive channel (MscL) in E. coli was studied with the aim of developing a strategy for statistical analysis based on hidden Markov models (HMMs) and determining the number of conductance levels of the channel, together with mean current, mean dwell time and equilibrium probability of occupancy for each level. The models incorporated state-dependent white noise and moving average adjustment for filtering, with maximum likelihood parameter estimates obtained using an EM (expectation-maximisation) based iteration. Adjustment for filtering was included as it could be expected that the electronic filter used in recording would have a major effect on obviously brief intermediate conductance level sojourns. Preliminary data analysis revealed that the brevity of intermediate level sojourns caused difficulties in assignment of data points to levels as a result of over-estimation of noise variances. When reasonable constraints were placed on these variances using the better determined noise variances for the closed and fully open levels, idealisation anomalies were eliminated. Nevertheless, simulations suggested that mean sojourn times for the intermediate levels were still considerably over-estimated, and that recording bandwidth was a major limitation; improved results were obtained with higher bandwidth data (10 kHz sampled at 25 kHz). The simplest model consistent with these data had four open conductance levels, intermediate levels being approximately 20%, 51% and 74% of fully open. The mean lifetime at the fully open level was about 1 ms; estimates for the three intermediate levels were 5492 mu s, probably still over-estimates. (c) 2005 Elsevier Inc. All rights reserved.
Keyword Biology
Mathematics, Interdisciplinary Applications
EM algorithm
filter approximation
hidden Markov models
patch clamp
state-dependent noise
Likelihood-ratio Tests
Patch-clamp Recordings
Probabilistic Functions
Observed Information
Speech Recognition
Em Algorithm
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 19 Sep 2007, 18:32:57 EST