High Resolution Ion Channel Dynamics
PD Dr. Indra Schröder

Our research interest lies in the biophysics of viral potassium channels. By a combination of electrophysiological and computational approaches we gain insight into the inner workings of these proteins.

Projects

  • Instability of the selectivity filter under ion depletion causes microsecond gating.
  • Unusual behaviour of Cesium block in different isoforms of viral channels is possibly linked to interaction on both the inner gate and selectivity filter regions.
  • Influence of the membrane environment on the channel protein.
Illustration of the gating behaviour and structure of the viral potassium channel Kcv. (Homology modelling was done by the group of S. Kast, TU Dortmund.)
Illustration of the gating behaviour and structure of the viral potassium channel Kcv. (Homology modelling was done by the group of S. Kast, TU Dortmund.)

(Sub)microsecond gating

Gating kinetics of single ion channels often take place beyond the instrumental resolution of the experiment. Our specialty is an analysis of the open channel noise that allows to reconstruct the statistics of these hidden events.

Why is this interesting?

  • Fast gating seems to take place mainly in the selectivity filter, the most crucial region of the protein.
  • Microsecond gating will be the first to be accurately predicted by Molecular Dynamics Simulations.

Ion channels often gate faster then can be directly resolved with the available recording bandwidth. The analysis with extended beta distributions allows to reconstruct the true single channel current in the open state and the rate constants of the fast gating from the filtered open channel noise.

The method is an extension of the beta distribution analysis developed by FitzHugh (1983) and Yellen (1984), which calculated the theoretical current distribution by analytical means, heavily relying on simplifying assumptions.

Our program “bownhill” greatly extends the applicability of the analysis by generating the theoretical current distributions via simulations. This allows the use of any Markov model, noise and filter characteristics. A review of the method and its application can be found in Schroeder (2015).

The program package (Windows(R) only), contains a short tutorial and sample files. Download “bownhilltutorial”. You are welcome to try out and use the program. If you use it in publications, please cite Schroeder, 2015, Channels. 9: 262-280.

References:

FitzHugh, R. 1983. Statistical properties of the asymmetric random telegraph signal, with applications to single-channel analysis. Math. Biosci. 89: 75–89.

Yellen, G. 1984. Ionic permeation and blockade in Ca2+-activated K+ channels of bovine chromaffin cells. J. Gen. Physiol. 84: 157–186.

Schroeder, I., and U.-P. Hansen. 2009a. Interference of shot noise of open-channel current with analysis of fast gating: patchers do not (yet) have to care. J. Membr. Biol. 229: 153–163.

Schroeder, I., and U.-P. Hansen. 2009b. Using a five-state model for fitting amplitude histograms from MaxiK channels: beta-distributions reveal more than expected. Eur. Biophys. J. 38: 1101–1114.

Schroeder, I. 2015. How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions. Channels. 9: 262–280.

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