Skip to main content
SpringerLink
Log in

Interference of Shot Noise of Open-Channel Current with Analysis of Fast Gating: Patchers do not (Yet) Have to Care

  • Published:
Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Microsecond gating of ion channels can be evaluated by fitting beta distributions to amplitude histograms of measured time series. The shape of these histograms is determined not only by the rate constants of the gating process (in relation to the filter frequency) but also by baseline noise and shot noise, resulting from the stochastic nature of ion flow. Under normal temporal resolution, the small shot noise can be ignored. This simplification may no longer be legitimate when rate constants reach the range above 1 μs−1. Here, the influence of shot noise is studied by means of simulated time series for several values of single-channel current of the fully open state and baseline noise. Under realistic optimal conditions (16 pA current, 1 pA noise, 50 kHz bandwidth), ignoring the shot noise leads to an underestimation of the rate constants above 1 μs−1 by a factor of about 2.5. However, in that range, the scatter of the evaluated rate constants is at least of the same magnitude, obscuring the systematic error. The incorporation of shot noise into the analysis will become more important when amplifiers with significantly reduced noise become available.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Ashcroft FM (2006) From molecule to malady. Nature 440:440–447

    Article  PubMed  CAS  Google Scholar 

  • Benndorf K (1995) Low noise recordings. In: Sackmann B, Neher E (eds) Single channel recordings, 2nd edn. Plenum Press, London, pp 129–145

    Google Scholar 

  • Bernèche S, Roux B (2005) A gate in the selectivity filter of potassium channels. Structure 13:91–560

    Article  Google Scholar 

  • Blatt MR (2004) Membrane transport in plants. Blackwell, Oxford

    Google Scholar 

  • Blunck R, Starace DM, Correa AM, Bezanilla F (2004) Detecting rearrangements of Shaker and NaChBac in real-time with fluorescence spectroscopy in patch-clamped mammalian cells. Biophys J 86:3966–3980

    Article  PubMed  CAS  Google Scholar 

  • Bortkewitsch VL (1898) Poissonverteilung über Pferdetritte bei preussischen Offizieren. Monatshefte Math 9:A39–A41

    Article  Google Scholar 

  • Brelidze TI, Niu X, Magleby KL (2003) A ring of eight conserved negatively charged amino acids doubles the conductance of BK channels and prevents inward rectification. Proc Natl Acad Sci USA 100:9017–9022

    Article  PubMed  CAS  Google Scholar 

  • Brunetti R, Affinito F, Jacoboni C, Piccinini E, Rudan M (2007) Shot noise in single open ion channels: a computational analysis approach based on atomistic simulations. J Comput Electron 6:391–394

    Article  CAS  Google Scholar 

  • Compoint M, Carloni P, Ramseyer C, Girardet C (2004) Molecular dynamics study of the KcsA channel at 2.0-Å resolution: stability and concerted motions within the pore. Biochim Biophys Acta 1661:26–39

    Article  PubMed  CAS  Google Scholar 

  • Devroye L (1986) Non-uniform random variate generation. Springer, New York. http://cg.scs.carleton.ca/~luc/rnbookindex.html. Accessed 19 Jan 2009

  • Doyle DA (2004) Molecular insights into ion channel function. Mol Membr Biol 21:221–225

    Article  PubMed  CAS  Google Scholar 

  • Fano U (1947) Ionization yield of radiation II. The fluctuations of the number of ions. Phys Rev 72:26–29

    Article  CAS  Google Scholar 

  • Farokhi A, Keunecke M, Hansen UP (2000) The anomalous mole fraction effect in Chara: gating at the edge of temporal resolution. Biophys J 79:3072–3082

    Article  PubMed  CAS  Google Scholar 

  • Feller W (1968) An introduction to probability theory and its applications, vol 1. John Wiley & Sons, New York

    Google Scholar 

  • Finkelstein A, Andersen OS (1981) The gramicidin A channel: a review of its permeability characteristics with special reference to the single-file aspect of transport. J Membr Biol 59:155–171

    Article  PubMed  CAS  Google Scholar 

  • FitzHugh R (1983) Statistical properties of the asymmetric random telegraph signal with application to single-channel analysis. Math Biosci 64:75–89

    Article  Google Scholar 

  • Freddolino PL, Liu F, Gruebele M, Schulten K (2008) Ten-microsecond molecular dynamics simulation of a fast-folding WW domain. Biophys J 94:L75–L77

    Article  PubMed  CAS  Google Scholar 

  • Frehland E (1978) Current noise around steady states in discrete transport systems. Biophys Chem 8:255–265

    Article  PubMed  CAS  Google Scholar 

  • Gillespie DT (1977) Exact stochastic simulation of coupled chemical reactions. J Phys Chem 81:2340–2361

    Article  CAS  Google Scholar 

  • Hansen UP, Gradmann D, Sanders D, Slayman CL (1981) Interpretation of current–voltage relationships for “active” ion transport systems: I. Steady-state reaction-kinetic analysis of class-I mechanisms. J Membr Biol 63:165–190

    Article  PubMed  CAS  Google Scholar 

  • Hansen UP, Tittor J, Gradmann D (1983) Interpretation of current–voltage relationships for “active” ion transport systems: II. Nonsteady-state reaction kinetic analysis of class I mechanisms with one slow time-constant. J Membr Biol 75:141–169

    Article  Google Scholar 

  • Hansen UP, Cakan O, Abshagen M, Farokhi A (2003) Gating models of the anomalous mole fraction effect of single-channel current in Chara. J Membr Biol 192:45–63

    Article  PubMed  CAS  Google Scholar 

  • Hedrich R, Marten I (2006) 30-year progress of membrane transport in plants. Planta 224:725–739

    Article  PubMed  CAS  Google Scholar 

  • Heinemann SH, Sigworth FJ (1988) Open channel noise. IV. Estimation of rapid kinetics of formamide block in gramicidin A channels. Biophys J 54:757–764

    Article  PubMed  CAS  Google Scholar 

  • Heinemann SH, Sigworth FJ (1990) Open channel noise. V. Fluctuating barriers to ion entry in gramicidin A channels. Biophys J 57:499–514

    Article  PubMed  CAS  Google Scholar 

  • Heinemann SH, Sigworth FJ (1991) Open channel noise. VI. Analysis of amplitude histograms to determine rapid kinetic parameters. Biophys J 60:577–587

    Article  PubMed  CAS  Google Scholar 

  • Huth T, Schmidtmayer J, Alzheimer C, Hansen UP (2008) 4-mode gating model of the inactivation of sodium channel Nav1.2a. Pfluegers Arch 457:103–119

    Article  CAS  Google Scholar 

  • Jeon J, Voth GA (2008) Gating of the mechanosensitive channel protein MscL: the interplay of membrane and protein. Biophys J 94:3497–3511

    Article  PubMed  CAS  Google Scholar 

  • Katz B, Miledi R (1970) Membrane noise produced by acetylcholine. Nature 226:962–963

    Article  PubMed  CAS  Google Scholar 

  • Kolb HA, Läuger P, Bamberg E (1975) Correlation analysis of electrical noise in lipid bilayer membranes: kinetics of gramicidin A channels. J Membr Biol 20:133–154

    Article  PubMed  CAS  Google Scholar 

  • Lehmann-Horn F, Jurkat-Rott K (1999) Voltage-gated ion channels and hereditary disease. Physiol Rev 79:1317–1372

    PubMed  CAS  Google Scholar 

  • Levis RA, Rae JL (1992) Constructing a patch clamp set up. Methods Enzymol 207:18–66

    Google Scholar 

  • Marsaglia G (2003) Random number generators. J Mod Appl Stat Methods 2:2–13

    Google Scholar 

  • Miloshevsky GV, Jordan PC (2008) Conformational changes in the selectivity filter of the open-state KcsA channel: an energy minimization study. Biophys J 95:3239–3251

    Article  PubMed  CAS  Google Scholar 

  • Neher E, Sakmann B (1976) Single-channel currents recorded from membrane of denervated frog muscle fibres. Nature 260:799–802

    Article  PubMed  CAS  Google Scholar 

  • Neher E, Stevens CF (1977) Conductance fluctuations and ionic pores in membranes. Annu Rev Biophys Bioeng 6:345–381

    Article  PubMed  CAS  Google Scholar 

  • Parzefall F, Wilhelm R, Heckmann M, Dudel J (1998) Single channel currents at six microsecond resolution elicited by acetylcholine in mouse myoballs. J Physiol 512:181–188

    Article  PubMed  CAS  Google Scholar 

  • Piccinini E, Affinito F, Brunetti R, Jacoboni C, Rudan M (2007) Computational analysis of current and noise properties of a single open ion channel. J Chem Theory Comput 3:248–255

    Article  CAS  Google Scholar 

  • Riessner T (1998) Level detection and extended beta distributions for the analysis of fast rate constants of Markov processes in sampled data. Shaker-Verlag, Aachen

    Google Scholar 

  • Schroeder I, Hansen UP (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. J Membr Biol 210:199–212

    Article  PubMed  CAS  Google Scholar 

  • Schroeder I, Hansen UP (2007) Saturation and μs-gating of current indicate depletion-induced instability of the MaxiK selectivity filter. J Gen Physiol 130:83–97

    Article  PubMed  Google Scholar 

  • Schroeder I, Hansen UP (2008) Tl+-induced μs-gating of current indicate instability of the MaxiK selectivity filter as caused by ion/protein interaction. J Gen Physiol 131:365–378

    Article  PubMed  CAS  Google Scholar 

  • Schroeder I, Huth T, Suitchmezian V, Jarosik J, Schnell S, Hansen UP (2004) Distributions-per-level: a means of testing level detectors and models of patch clamp data. J Membr Biol 197:49–58

    Article  CAS  Google Scholar 

  • Schottky W (1918) Über spontane Stromschwankungen in verschiedenen Elektrizitätsleitern. Annu Phys (Leipzig) 57:541–567

    Article  Google Scholar 

  • Sigworth F (1985) Open channel noise. I. Noise in acetylcholine receptor currents suggests conformational fluctuations. Biophys J 47:709–720

    Article  PubMed  CAS  Google Scholar 

  • Sigworth F, Urry DW, Prasad KU (1987) Open channel noise. III. High-resolution recordings show rapid current fluctuations in gramicidin A and four chemical analogues. Biophys J 52:1055–1064

    Article  PubMed  CAS  Google Scholar 

  • Tayefeh S, Kloss T, Thiel G, Hertel B, Moroni A, Kast SM (2007) Molecular dynamics simulation of the cytosolic mouth in Kcv-type potassium channels. Biochemistry 46:4826–4839

    Article  PubMed  CAS  Google Scholar 

  • Walden M, Accardi A, Wu F, Xu C, Williams C, Miller C (2007) Uncoupling and turnover in a Cl−/H+ exchange transporter. J Gen Physiol 129:317–329

    Article  PubMed  CAS  Google Scholar 

  • Weise R, Gradmann D (2000) Effects of Na+ on the predominant K+ channel in the tonoplast of Chara: decrease of conductance by blocks in 100 ns range and induction of oligo- or poly-subconductance gating modes. J Membr Biol 175:87–93

    Article  PubMed  CAS  Google Scholar 

  • White PJ, Ridout MS (1998) The estimation of rapid rate constants from current–amplitude frequency distributions of single-channel recordings. J Membr Biol 161:115–129

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported by the Deutsche Forschungsgemeinschaft (Ha712/14-3). We are grateful to Prof. Dr. Axel Scheidig for continuous support of our work.

Author information

Authors and Affiliations

  1. Department of Structural Biology, University of Kiel, Leibnizstr. 11, 24098, Kiel, Germany

    Indra Schroeder & Ulf-Peter Hansen

Authors
  1. Indra Schroeder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ulf-Peter Hansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulf-Peter Hansen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schroeder, I., Hansen, UP. Interference of Shot Noise of Open-Channel Current with Analysis of Fast Gating: Patchers do not (Yet) Have to Care. J Membrane Biol 229, 153–163 (2009). https://doi.org/10.1007/s00232-009-9183-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-009-9183-3

Keywords

Search

Navigation