ArticleThe Journal of physiology2003
The quality of maximum likelihood estimates of ion channel rate constants.
Article in The Journal of physiology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 113 citations in OpenAlex.
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- Mechanism of pore opening in the calcium-activated chloride channel TMEM16A.Nature communications · 2021Article
- Obtaining transition rates from single-channel data without initial parameter seeding.Channels (Austin, Tex.) · 2020Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- A HIDDEN MARKOV MODEL APPROACH TO CHARACTERIZING THE PHOTO-SWITCHING BEHAVIOR OF FLUOROPHORES.The annals of applied statistics · 2019Article
- High bandwidth approaches in nanopore and ion channel recordings - A tutorial review.Analytica chimica acta · 2019Review
- Spatiotemporal relationships defining the adaptive gating of the bacterial mechanosensitive channel MscS.European biophysics journal : EBJ · 2018Article
- A structurally derived model of subunit-dependent NMDA receptor function.The Journal of physiology · 2018Article
- Estimating kinetic mechanisms with prior knowledge II: Behavioral constraints and numerical tests.The Journal of general physiology · 2018Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Properties of maximum likelihood estimators of rate constants for channel mechanisms are investigated, to see what can and cannot be inferred from experimental results. The implementation of the HJCFIT method is described; it maximises the likelihood of an entire sequence of apparent open and shut times, with the rate constants in a specified reaction mechanism as free parameters. The exact method for missed brief events is used. Several methods for testing the quality of the fit are described. The distributions of rate constants, and correlations between them, are investigated by doing sets of 1000 fits to simulated experiments. In a standard nicotinic receptor mechanism, all nine free rate constants can be estimated even from one single channel recording, as long as the two binding sites are independent, even when the number of channels in the patch is not known. The estimates of rate constants that apply to diliganded channels are robust; good estimates can be obtained even with erroneous assumptions (e.g. about the value of a fixed rate constant or the independence of sites). Rate constants that require distinction between the two sites are less robust, and require that an EC50 be specified, or that records at two concentrations be fitted simultaneously. Despite the complexity of the problem, it appears that there exist two solutions with very similar likelihoods, as in the simplest case. The hazards that result from this, and from the strong positive correlation between estimates of opening and shutting rates, are discussed.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.