How to resolve microsecond current fluctuations in single ion channels: The power of beta distributions

Abstract

A main ingredient for the understanding of structure/function correlates of ion channels is the quantitative description of single-channel gating and conductance. However, a wealth of information provided from fast current fluctuations beyond the temporal resolution of the recording system is often ignored, even though it is close to the time window accessible to molecular dynamics simulations. This kind of current fluctuations provide a special technical challenge, because individual opening/closing or blocking/unblocking events cannot be resolved, and the resulting averaging over undetected events decreases the single-channel current. Here, I briefly summarize the history of fast-current fluctuation analysis and focus on the so-called “beta distributions.” This tool exploits characteristics of current fluctuation-induced excess noise on the current amplitude histograms to reconstruct the true single-channel current and kinetic parameters. A guideline for the analysis and recent applications demonstrate that a construction of theoretical beta distributions by Markov Model simulations offers maximum flexibility as compared to analytical solutions.

Keywords:

• β
• distribution
• fast block
• fast current fluctuations
• fast gating
• flickery gating
• open-channel noise
• rate constants
• skewed amplitude histogram
• true single-channel current

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

I am grateful to Oliver Rauh for the permission to use the raw data of Kcv_S and Kcv_NTS, to Anna Moroni for the data of Kcv_PBCV-1 and Annemarie Donoghue, née Brauser for the data of OmpF. Ulf-Peter Hansen and Gerhard Thiel provided helpful discussion.

Funding

The work was funded by DFG grant SCHR 1467/1-1 to I. Schroeder.