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Estimation of ion channel kinetics from fluctuations of macroscopic currents.
Moffatt, Luciano.
Afiliação
  • Moffatt L; Instituto de Química Física de los Materiales, Medio Ambiente y Energía, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. lmoffatt@qi.fcen.uba.ar
Biophys J ; 93(1): 74-91, 2007 Jul 01.
Article em En | MEDLINE | ID: mdl-17416622
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Canais Iônicos / Modelos Biológicos / Modelos Químicos Tipo de estudo: Health_economic_evaluation / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Biophys J Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ativação do Canal Iônico / Canais Iônicos / Modelos Biológicos / Modelos Químicos Tipo de estudo: Health_economic_evaluation / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Biophys J Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos