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Strengths and limits of Beta distributions as a means of reconstructing the true single-channel current in patch clamp time series with fast gating.

Schroeder, I. ; Hansen, U.-P. (2006)
Strengths and limits of Beta distributions as a means of reconstructing the true single-channel current in patch clamp time series with fast gating.
In: The Journal of Membrane Biology, 210 (3)
Artikel, Bibliographie

Kurzbeschreibung (Abstract)

Single-channel current seems to be one of the most obvious characteristics of ion transport. But in some cases, its determination is more complex than anticipated at first glance. Problems arise from fast gating in time series of patch-clamp current, which can lead to a reduced apparent (measured) single-channel current. Reduction is caused by undetected averaging over closed and open intervals in the anti-aliasing filter. Here it is shown that fitting the measured amplitude histograms by Beta distributions is an efficient tool of reconstructing the true current level from measured data. This approach becomes even more powerful when it is applied to amplitude distributions-per-level. Simulated time series are employed to show that the error sum is a good guideline for finding the correct current level. Furthermore, they show that a Markov model smaller than the one used for gating analysis can be used for current determination (mostly O-C, i.e., open-closed). This increases the reliability of the Beta fit. The knowledge of the true current level is not only important for the understanding of the biophysical properties of the channel. It is also a prerequisite for the correct determination of the rate constants of gating. The approach is applied to measured data. The examples reveal the limits of the analysis imposed by the signal-to-noise ratio and the shape of the amplitude distribution. One application shows that the negative slope of the I-V curve of the human MaxiK channel expressed in HEK293 cells is caused by fast gating.

Typ des Eintrags: Artikel
Erschienen: 2006
Autor(en): Schroeder, I. ; Hansen, U.-P.
Art des Eintrags: Bibliographie
Titel: Strengths and limits of Beta distributions as a means of reconstructing the true single-channel current in patch clamp time series with fast gating.
Sprache: Englisch
Publikationsjahr: 2006
Titel der Zeitschrift, Zeitung oder Schriftenreihe: The Journal of Membrane Biology
Jahrgang/Volume einer Zeitschrift: 210
(Heft-)Nummer: 3
Kurzbeschreibung (Abstract):

Single-channel current seems to be one of the most obvious characteristics of ion transport. But in some cases, its determination is more complex than anticipated at first glance. Problems arise from fast gating in time series of patch-clamp current, which can lead to a reduced apparent (measured) single-channel current. Reduction is caused by undetected averaging over closed and open intervals in the anti-aliasing filter. Here it is shown that fitting the measured amplitude histograms by Beta distributions is an efficient tool of reconstructing the true current level from measured data. This approach becomes even more powerful when it is applied to amplitude distributions-per-level. Simulated time series are employed to show that the error sum is a good guideline for finding the correct current level. Furthermore, they show that a Markov model smaller than the one used for gating analysis can be used for current determination (mostly O-C, i.e., open-closed). This increases the reliability of the Beta fit. The knowledge of the true current level is not only important for the understanding of the biophysical properties of the channel. It is also a prerequisite for the correct determination of the rate constants of gating. The approach is applied to measured data. The examples reveal the limits of the analysis imposed by the signal-to-noise ratio and the shape of the amplitude distribution. One application shows that the negative slope of the I-V curve of the human MaxiK channel expressed in HEK293 cells is caused by fast gating.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
Hinterlegungsdatum: 25 Okt 2012 11:50
Letzte Änderung: 02 Nov 2018 10:36
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