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.)

(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.

Jump to: 2021 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2009 | 2008 | 2007 | 2006
Number of items: 31.

2021

Winterstein, Laura-Marie and Kukovetz, Kerri and Hansen, Ulf-Peter and Schroeder, Indra and Van Etten, James L. and Moroni, Anna and Thiel, Gerhard and Rauh, Oliver (2021):
Distinct lipid bilayer compositions have general and protein-specific effects on K+ channel function.
In: The Journal of general physiology, 153 (2), pp. e202012731. ISSN 1540-7748,
DOI: 10.1085/jgp.202012731,
[Article]

Schmidt, Michael and Schroeder, Indra and Bauer, Daniel and Thiel, Gerhard and Hamacher, Kay (2021):
Inferring functional units in ion channel pores via relative entropy.
In: European biophysics journal : EBJ, ISSN 1432-1017,
DOI: 10.1007/s00249-020-01480-7,
[Article]

2019

Eckert, Denise and Schulze, Tobias and Stahl, Julian and Rauh, Oliver and Van Etten, James L. and Hertel, Brigitte and Schroeder, Indra and Moroni, Anna and Thiel, Gerhard (2019):
A small viral potassium ion channel with an inherent inward rectification.
In: Channels (Austin, Tex.), 13 (1), pp. 124-135. ISSN 1933-6969,
[Article]

Hartel, Andreas J. W. and Shekar, Siddharth and Ong, Peijie and Schroeder, Indra and Thiel, Gerhard and Shepard, Kenneth L. (2019):
High bandwidth approaches in nanopore and ion channel recordings - A tutorial review.
In: Analytica chimica acta, 1061, pp. 13-27. ISSN 1873-4324,
DOI: 10.1016/j.aca.2019.01.034,
[Article]

2018

Rondelli, V. and Del Favero, E. and Brocca, P. and Fragneto, G. and Trapp, M. and Mauri, L. and Ciampa, M. G. and Romani, G. and Braun, C. J. and Winterstein, L. and Schroeder, Indra and Thiel, Gerhard and Moroni, Anna and Cantu', L. (2018):
Directional K+ channel insertion in a single phospholipid bilayer: Neutron reflectometry and electrophysiology in the joint exploration of a model membrane functional platform.
In: Biochimica et biophysica acta, 1862 (8), pp. 1742-1750. ISSN 0006-3002,
[Article]

Rauh, O. and Hansen, U. P. and Scheub, D. D. and Thiel, Gerhard and Schroeder, Indra (2018):
Site-specific ion occupation in the selectivity filter causes voltage-dependent gating in a viral K+ channel.
In: Scientific reports, 8 (1), p. 10406. ISSN 2045-2322,
[Article]

Winterstein, Laura-Marie and Kukovetz, Kerri and Rauh, Oliver and Turman, Daniel L. and Braun, Christian and Moroni, Anna and Schroeder, Indra and Thiel, Gerhard (2018):
Reconstitution and functional characterization of ion channels from nanodiscs in lipid bilayers.
In: The Journal of general physiology, 150 (4), pp. 637-646. ISSN 1540-7748,
[Article]

Hartel, Andreas J. W. and Ong, Peijie and Schroeder, Indra and Giese, M. Hunter and Shekar, Siddharth and Clarke, Oliver B. and Zalk, Ran and Marks, Andrew R. and Hendrickson, Wayne A. and Shepard, Kenneth L. (2018):
Single-channel recordings of RyR1 at microsecond resolution in CMOS-suspended membranes.
In: Proceedings of the National Academy of Sciences, 115 (8), pp. E1789-E1798. National Academy of Sciences, ISSN 0027-8424,
DOI: 10.1073/pnas.1712313115,
[Article]

2017

Rauh, O. and Hansen, U. P. and Mach, S. and Hartel, A. J. W. and Shepard, K. L. and Thiel, Gerhard and Schroeder, Indra (2017):
Extended beta distributions open the access to fast gating in bilayer experiments: assigning the voltage-dependent gating to the selectivity filter.
In: FEBS letters, 591 (23), pp. 3850-3860. ISSN 1873-3468,
[Article]

Rauh, Oliver and Urban, Martin and Henkes, Leonhard M. and Winterstein, Tobias and Greiner, Timo and Van Etten, James L. and Moroni, Anna and Kast, Stefan M. and Thiel, Gerhard and Schroeder, Indra (2017):
Identification of Intrahelical Bifurcated H-Bonds as a New Type of Gate in K(+) Channels.
In: Journal of the American Chemical Society, 139 (22), pp. 7494-7503. ISSN 1520-5126,
[Article]

Baumeister, Dirk and Hertel, Brigitte and Schroeder, Indra and Gazzarrini, Sabrina and Kast, Stefan M. and Van Etten, James L. and Moroni, Anna and Thiel, Gerhard (2017):
Conversion of an instantaneous activating K(+) channel into a slow activating inward rectifier.
In: FEBS letters, 591 (2), pp. 295-303. ISSN 1873-3468,
[Article]

Rauh, Oliver and Hansen, Ulf-Peter and Mach, Sebastian and Hartel, Andreas J.W. and Shepard, Kenneth L. and Thiel, Gerhard and Schroeder, Indra (2017):
Extended beta distributions open the access to fast gating in bilayer experiments-assigning the voltage-dependent gating to the selectivity filter.
In: FEBS Letters, 591 (23), pp. 3850-3860. Wiley-Blackwell, ISSN 00145793,
DOI: 10.1002/1873-3468.12898,
[Article]

2016

Hansen, Ulf-Peter and Rauh, Oliver and Schroeder, Indra (2016):
A simple recipe for setting up the flux equations of cyclic and linear reaction schemes of ion transport with a high number of states: The arrow scheme.
In: Channels, 10 (2), pp. 119-138. Taylor & Francis, ISSN 1933-6950,
DOI: 10.1080/19336950.2015.1120391,
[Article]

2015

Gibhardt, Christine S. and Roth, Bastian and Schroeder, Indra and Fuck, Sebastian and Becker, Patrick and Jakob, Burkhard and Fournier, Claudia and Moroni, Anna and Thiel, Gerhard (2015):
X-ray irradiation activates K(+) channels via H2O2 signaling.
In: Scientific reports, 5, p. 13861. ISSN 2045-2322,
[Article]

Schroeder, Indra (2015):
How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions.
In: Channels, 9 (5), pp. 262-280. Taylor & Francis, ISSN 1933-6950,
DOI: 10.1080/19336950.2015.1083660,
[Article]

2014

Lolicato, Marco and Bucchi, Annalisa and Arrigoni, Cristina and Zucca, Stefano and Nardini, Marco and Schroeder, Indra and Simmons, Katie and Aquila, Marco and DiFrancesco, Dario and Bolognesi, Martino and Schwede, Frank and Kashin, Dmitry and Fishwick, Colin W. G. and Johnson, A . Peter and Thiel, Gerhard and Moroni, Anna (2014):
Cyclic dinucleotides bind the C-linker of HCN4 to control channel cAMP responsiveness.
In: Nature chemical biology, 10 (6), pp. 457-462. ISSN 1552-4469,
[Article]

Difrancesco, Mattia L. and Hansen, Ulf-Peter and Thiel, Gerhard and Moroni, Anna and Schroeder, Indra (2014):
Effect of Cytosolic pH on Inward Currents Reveals Structural Characteristics of the Proton Transport Cycle in the Influenza A Protein M2 in Cell-Free Membrane Patches of Xenopus oocytes.
In: PloS one, 9 (9), pp. e107406. ISSN 1932-6203,
[Article]

Siotto, Fenja and Martin, Corinna and Rauh, Oliver and Van Etten, James L. and Schroeder, Indra and Moroni, Anna and Thiel, Gerhard (2014):
Viruses infecting marine picoplancton encode functional potassium ion channels.
In: Virology, 466-467, pp. 103-11. ISSN 1096-0341,
[Article]

2013

Arrigoni, Cristina and Schroeder, Indra and Romani, Giulia and Van Etten, James L. and Thiel, Gerhard and Moroni, Anna (2013):
The voltage-sensing domain of a phosphatase gates the pore of a potassium channel.
In: The Journal of general physiology, 141 (3), pp. 389-95. ISSN 1540-7748,
[Article]

Schroeder, Indra and Thiel, Gerhard and Hansen, Ulf-Peter (2013):
Ca2+ block and flickering both contribute to the negative slope of the IV curve in BK channels.
In: The Journal of general physiology, 141 (4), pp. 499-505. ISSN 1540-7748,
[Article]

Schroeder, Indra and Gazzarrini, Sabrina and Ferrara, Giuseppina and Thiel, Gerhard and Hansen, Ulf-Peter and Moroni, Anna (2013):
Creation of a reactive oxygen species-insensitive Kcv channel.
In: Biochemistry, 52 (18), pp. 3130-7. ISSN 1520-4995,
[Article]

Braun, Christian and Lachnit, Christine and Becker, Patrick and Henkes, Leonhard M. and Arrigoni, Cristina and Kast, Stefan M. and Moroni, Anna and Thiel, Gerhard and Schroeder, Indra (2013):
Viral potassium channels as a robust model system for studies of membrane-protein interaction.
In: Biochimica et biophysica acta, 1838 (4), pp. 1096-1103. ISSN 0006-3002,
[Article]

Braun, Christian and Schroeder, Indra and Henkes, Leonhard M. and Arrigoni, Cristina and Kast, Stefan M. and Moroni, Anna and Thiel, Gerhard (2013):
Minimal viral K plus channels as robust model systems for understanding structure/function correlations.
In: European biophysics journal : EBJ, 42 (Suppl. 1), pp. S79. ISSN 0175-7571,
[Article]

2012

Brauser, Annemarie and Schroeder, Indra and Gutsmann, Thomas and Cosentino, Cristian and Moroni, Anna and Hansen, Ulf-Peter and Winterhalter, Mathias (2012):
Modulation of enrofloxacin binding in OmpF by Mg2+ as revealed by the analysis of fast flickering single-porin current.
In: The Journal of General Physiology, 140 (1), pp. 69-82. ISSN 1540-7748,
[Article]

2011

Thiel, Gerhard and Baumeister, Dirk and Schroeder, Indra and Kast, Stefan M. and Van Etten, James L. and Moroni, Anna (2011):
Minimal art: or why small viral K(+) channels are good tools for understanding basic structure and function relations.
In: Biochimica et biophysica acta, 1808 (2), pp. 580-8. ISSN 0006-3002,
[Article]

2009

Abenavoli, Alessandra and DiFrancesco, Mattia Lorenzo and Schroeder, Indra and Epimashko, Svetlana and Gazzarrini, Sabrina and Hansen, Ulf Peter and Thiel, Gerhard and Moroni, Anna (2009):
Fast and slow gating are inherent properties of the pore module of the K+ channel Kcv.
In: The Journal of general physiology, 134 (3), pp. 219-29. ISSN 1540-7748,
[Article]

Schroeder, Indra and Hansen, Ulf-Peter (2009):
Using a five-state model for fitting amplitude histograms from MaxiK channels: beta-distributions reveal more than expected.
In: European biophysics journal : EBJ, 38 (8), pp. 1101-14. ISSN 1432-1017,
[Article]

Schroeder, Indra and Hansen, Ulf-Peter (2009):
Interference of shot noise of open-channel current with analysis of fast gating: patchers do not (Yet) have to care.
In: The Journal of Membrane Biology, 229 (3), pp. 153-63. ISSN 1432-1424,
[Article]

2008

Schroeder, Indra and Hansen, Ulf-Peter (2008):
Tl+-induced micros gating of current indicates instability of the MaxiK selectivity filter as caused by ion/pore interaction.
In: The Journal of General Physiology, 131 (4), pp. 365-78. ISSN 1540-7748,
[Article]

2007

Schroeder, Indra and Hansen, Ulf-Peter (2007):
Saturation and microsecond gating of current indicate depletion-induced instability of the MaxiK selectivity filter.
In: The Journal of General Physiology, 130 (1), pp. 83-97. ISSN 0022-1295,
[Article]

2006

Huth, Tobias and Schroeder, Indra and Hansen, Ulf-Peter (2006):
The power of two-dimensional dwell-time analysis for model discrimination, temporal resolution, multichannel analysis and level detection.
In: The Journal of Membrane Biology, 214 (1), pp. 19-32. ISSN 0022-2631,
[Article]

This list was generated on Wed Feb 24 03:46:23 2021 CET.