Estimation of ion channel kinetics from fluctuations of macroscopic currents

For single channel recordings, the maximum likelihood estimation (MLE) of kinetic rates and conductance is well established. A direct extrapolation of this method to macroscopic currents is computationally prohibitive: it scales as a power of the number of channels. An approximated MLE that ignored...

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Publicado: 2007
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v93_n1_p74_Moffatt
http://hdl.handle.net/20.500.12110/paper_00063495_v93_n1_p74_Moffatt
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spelling paper:paper_00063495_v93_n1_p74_Moffatt2023-06-08T14:31:18Z Estimation of ion channel kinetics from fluctuations of macroscopic currents ion channel accuracy algorithm analytical error article correlation analysis ion conductance kinetics maximum likelihood method reliability simulation stimulation white noise For single channel recordings, the maximum likelihood estimation (MLE) of kinetic rates and conductance is well established. A direct extrapolation of this method to macroscopic currents is computationally prohibitive: it scales as a power of the number of channels. An approximated MLE that ignored the local time correlation of the data has been shown to provide estimates of the kinetic parameters. In this article, an improved approximated MLE that takes into account the local time correlation is proposed. This method estimates the channel kinetics using both the time course and the random fluctuations of the macroscopic current generated by a homogeneous population of ion channels under white noise. It allows arbitrary kinetic models and stimulation protocols. The application of the proposed algorithm to simulated data from a simple three-state model on nonstationary conditions showed reliable estimates of all the kinetic constants, the conductance and the number of channels, and reliable values for the standard error of those estimates. Compared to the previous approximated MLE, it reduces by a factor of 10 the amount of data needed to secure a given accuracy and it can even determine the kinetic rates in macroscopic stationary conditions. © 2007 by the Biophysical Society. 2007 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v93_n1_p74_Moffatt http://hdl.handle.net/20.500.12110/paper_00063495_v93_n1_p74_Moffatt
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic ion channel
accuracy
algorithm
analytical error
article
correlation analysis
ion conductance
kinetics
maximum likelihood method
reliability
simulation
stimulation
white noise
spellingShingle ion channel
accuracy
algorithm
analytical error
article
correlation analysis
ion conductance
kinetics
maximum likelihood method
reliability
simulation
stimulation
white noise
Estimation of ion channel kinetics from fluctuations of macroscopic currents
topic_facet ion channel
accuracy
algorithm
analytical error
article
correlation analysis
ion conductance
kinetics
maximum likelihood method
reliability
simulation
stimulation
white noise
description For single channel recordings, the maximum likelihood estimation (MLE) of kinetic rates and conductance is well established. A direct extrapolation of this method to macroscopic currents is computationally prohibitive: it scales as a power of the number of channels. An approximated MLE that ignored the local time correlation of the data has been shown to provide estimates of the kinetic parameters. In this article, an improved approximated MLE that takes into account the local time correlation is proposed. This method estimates the channel kinetics using both the time course and the random fluctuations of the macroscopic current generated by a homogeneous population of ion channels under white noise. It allows arbitrary kinetic models and stimulation protocols. The application of the proposed algorithm to simulated data from a simple three-state model on nonstationary conditions showed reliable estimates of all the kinetic constants, the conductance and the number of channels, and reliable values for the standard error of those estimates. Compared to the previous approximated MLE, it reduces by a factor of 10 the amount of data needed to secure a given accuracy and it can even determine the kinetic rates in macroscopic stationary conditions. © 2007 by the Biophysical Society.
title Estimation of ion channel kinetics from fluctuations of macroscopic currents
title_short Estimation of ion channel kinetics from fluctuations of macroscopic currents
title_full Estimation of ion channel kinetics from fluctuations of macroscopic currents
title_fullStr Estimation of ion channel kinetics from fluctuations of macroscopic currents
title_full_unstemmed Estimation of ion channel kinetics from fluctuations of macroscopic currents
title_sort estimation of ion channel kinetics from fluctuations of macroscopic currents
publishDate 2007
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00063495_v93_n1_p74_Moffatt
http://hdl.handle.net/20.500.12110/paper_00063495_v93_n1_p74_Moffatt
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