How Powerful is the Dwell-Time Analysis of Multichannel Records? |
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Authors: | R Blunck U Kirst T Riessner U-P Hansen |
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Institution: | (1) Institute of Applied Physics, University of Kiel, 24098 Kiel, Germany, DE |
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Abstract: | Exact algorithms for the kinetic analysis of multichannel patch-clamp records require hours to days for a single record.
Thus, it may be reasonable to use a fast but less accurate method for the analysis of all data sets and to use the results
for a reanalysis of some selected records with more sophisticated approaches. For the first run, the tools of single-channel
analysis were used for the evaluation of the single-channel rate constants from multichannel dwell-time histograms. This could
be achieved by presenting an ensemble of single channels by a ``macrochannel' comprising all possible states of the ensemble
of channels. Equations for the calculations of the elements of the macrochannel transition matrix and for the steady-state
concentrations for individual states are given. Simulations of multichannel records with 1 to 8 channels with two closed and
one open states and with 2 channels with two open and two closed states were done in order to investigate under which conditions
the one-dimensional dwell-time analysis itself already provides reliable results. Distributions of the evaluated single-channel
rate constants show that a bias of the estimations of the single-channel rate constants of 10 to 20% has to be accepted. The
comparison of simulations with signal-to-noise ratios of SNR = 1 or SNR = 25 demonstrates that the major problem is not the
convergence of the fitting routine, but failures of the level detector algorithm which creates the dwell-times distributions
from noisy time series.
The macrochannel presentation allows the incorporation of constraints like channel interaction. The evaluation of simulated
4-channel records in which the rate-constant of opening increased by 20% per already open channel could reveal the interaction
factor.
Received: 9 June 1997/Revised: 28 April 1998 |
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Keywords: | : Channel interaction — Dwell-time histograms — Markov process — Rate constants — Target-fit |
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