ArticleBiophysical journal2004
Use of the covariance matrix in directly fitting kinetic parameters: application to GABAA receptors.
Article in Biophysical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Article
- Computer modeling of whole-cell voltage-clamp analyses to delineate guidelines for good practice of manual and automated patch-clamp.Scientific reports · 2021Article
- Calibration of ionic and cellular cardiac electrophysiology models.Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Association of Model Neurotransmitters with Lipid Bilayer Membranes.Biophysical journal · 2020Article
- Estimating kinetic mechanisms with prior knowledge I: Linear parameter constraints.The Journal of general physiology · 2018Article
- Identifiability, reducibility, and adaptability in allosteric macromolecules.The Journal of general physiology · 2017Article
- Elucidation of molecular kinetic schemes from macroscopic traces using system identification.PLoS computational biology · 2017Article
- Exploring the mechanism of general anesthesia: kinetic analysis of GABAA receptor electrophysiology.Biophysical journal · 2015Article
- Determination of parameter identifiability in nonlinear biophysical models: A Bayesian approach.The Journal of general physiology · 2014Article
- Methods for quantification of pore-voltage sensor interaction in Ca(V)1.2.Pflugers Archiv : European journal of physiology · 2014Article
- Maximum likelihood estimation of biophysical parameters of synaptic receptors from macroscopic currents.Frontiers in cellular neuroscience · 2014Article
- Efficient maximum likelihood estimation of kinetic rate constants from macroscopic currents.PloS one · 2011Article
- A modeling study of T-type Ca2+ channel gating and modulation by L-cysteine in rat nociceptors.Biophysical journal · 2010Article
- Determining the neurotransmitter concentration profile at active synapses.Molecular neurobiology · 2009Review
- Real-time kinetic modeling of voltage-gated ion channels using dynamic clamp.Biophysical journal · 2008Article
- Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABAA receptor desensitization and deactivation.The Journal of physiology · 2007Article
- Statistical properties of ion channel records. Part II: estimation from the macroscopic current.Mathematical biosciences · 2007Article
- Statistical properties of ion channel records. Part I: relationship to the macroscopic current.Mathematical biosciences · 2007Article
- Estimation of ion channel kinetics from fluctuations of macroscopic currents.Biophysical journal · 2007Article
- The ion channel inverse problem: neuroinformatics meets biophysics.PLoS computational biology · 2006Review
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Authors and funding
2 authors.
Funding
Abstract
A new method of analysis is described that begins to explore the relationship between the phases of ion channel desensitization and the underlying states of the channel. The method, referred to as covariance fitting (CVF), couples Q-matrix calculations with a maximum likelihood algorithm to fit macroscopic desensitization data directly to kinetic models. Unlike conventional sum-of-squares minimization, CVF fits both the magnitude of the recorded current and the strength of the correlations between different time points. When applied to simulated data generated using various kinetic models with up to 11 free parameters, CVF leads to reasonable parameter estimates. Coupled with the likelihood ratio test, it accurately discriminates between models with different numbers of states, discriminates between most models with the same number but a different arrangement of states, and extracts meaningful information on the relationship between the desensitized states and the phases of macroscopic desensitization. When applied to GABA(A) receptor traces (outside out patches, alpha 1 beta 2 gamma 2S, 1 mM GABA, >2.5 s), a model with two open states and three desensitized states is favored. When applied to simulated data generated using a consensus model, CVF leads to reasonable parameter estimates and accurately discriminates between this and other models.
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