title: Hidden Markov analysis of mechanosensitive ion channel gating.
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 54-92 micros, probably still over-estimates.
authors.affiliation: School of Mathematics and Statistics, The University of Western Australia, Crawley 6009, Australia. nazim@maths.uwa.edu.au
authors.forename: R Nazim
authors.initials: RN
authors.lastname: Khan
authors.forename: Boris
authors.initials: B
authors.lastname: Martinac
authors.forename: Barry W
authors.initials: BW
authors.lastname: Madsen
authors.forename: Robin K
authors.initials: RK
authors.lastname: Milne
authors.forename: Geoffrey F
authors.initials: GF
authors.lastname: Yeo
authors.forename: Robert O
authors.initials: RO
authors.lastname: Edeson
mesh_terms: D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008390:Markov Chains; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D018408:Patch-Clamp Techniques
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli