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Numerical evaluation of observed sojourn time distributions for a single ion channel incorporating time interval omission

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Abstract

The dynamical aspects of single ion channel gating can be modelled by a semi-Markov process. There is aggregation of states, corresponding to the receptor channel being open or closed, and there is time interval omission, brief sojourns in either the open or closed classes of states not being detected. This paper is concerned with the computation of the probability density functions of observed open (closed) sojourn-times incorporating time interval omission. A system of Volterra integral equations is derived, whose solution governs the required density function. Numerical procedures, using iterative and multistep methods, are described for solving these equations. Examples are given, and in the special case of Markov models results are compared with those obtained by alternative methods. Probabilistic interpretations are given for the iterative methods, which also give lower bounds for the solutions.

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References

  • Ball, F. G. and Davies, S. S. (1992) Statistical inference for a two-state Markov model of a single ion channel, incorporating time interval omission. Technical Report 92-9, Nottingham Statistics Group.

  • Ball, F. G. and Sansom, M. S. P. (1988) Aggregated Markov processes incorporating time interval omission. Advances in Applied Probability, 20, 546–572.

    Google Scholar 

  • Ball, F. G., Davies, S. S. and Sansom, M. S. P. (1990) Singlechannel data and missed events: analysis of a two-state Markov model. Proceedings of the Royal Society of London B, 242, 61–67.

    Google Scholar 

  • Ball, F. G., Milne, R. K. and Yeo, G. F. (1991) Aggregated semi-Markov processes incorporating time interval omission. Advances in Applied Probability, 23, 772–797.

    Google Scholar 

  • Ball, F. G., Yeo, G. F., Milne, R. K., Edeson, R. O., Madsen, B. W. and Sansom, M. S. P. (1993a) Single ion channel models incorporating aggregation and time interval omission. Biophysical Journal, 64, 357–374.

    Google Scholar 

  • Ball, F. G., Milne, R. K. and Yeo, G. F. (1993b) On the exact distribution of observed open times in single channel models. Journal of Applied Probability, 30, 529–537.

    Google Scholar 

  • Blatz, A. L. and Magleby, K. L. (1986) Correcting single channel data for missed events. Biophysical Journal, 49, 967–980.

    Google Scholar 

  • Çinlar, E. (1969) Markov renewal theory. Advances in Applied Probability, 1, 123–187.

    Google Scholar 

  • Çinlar, E. (1975) Introduction to Stochastic Processes. Prentice-Hall, Englewood Cliffs, NJ.

    Google Scholar 

  • Clarke, B. R., Milne, R. K. and Yeo, G. F. (1993) Local asymptotic theory for multiple solutions of likelihood equations, with applications to a single ion channel model. Scandinavian Journal of Statistics, 20, 133–146.

    Google Scholar 

  • Colquhoun, D. and Hawkes, A. G. (1977) Relaxation and fluctuations of membrane currents that flow through drug-operated channels. Proceedings of the Royal Society of London B, 199, 231–262.

    Google Scholar 

  • Colquhoun, D. and Hawkes, A. G. (1982) On the stochastic properties of bursts of single ion channel openings and of cluster of bursts. Philosophical Transactions of the Royal Society of London B, 300, 1–59.

    Google Scholar 

  • Colquhoun, D. and Sigworth, F. J. (1983) Fitting and statistical analysis of single-channel records. In Single-Channel Recording (B. Sakman and E. Neher, eds.), pp. 135–175. Plenum Press, New York.

    Google Scholar 

  • Delves, L. M. and Mohamed, J. L. (1985) Computation Methods for Integral Equations. Cambridge University Press.

  • Edeson, R. O., Yeo, G. F., Milne, R. K. and Madsen, B. W. (1990) Graphs, random sums, and sojourn time distributions, with application to ion-channel modeling. Mathematical Biosciences, 102, 75–104.

    Google Scholar 

  • Feller, W. (1971) An Introduction to Probability Theory and its Applications, Vol II, 2nd edn. Wiley, New York.

    Google Scholar 

  • Fredkin, D. R., Montal, M. and Rice, J. A. (1985) Identification of aggregated Markovian models: application to the nicotinic acetylcholine receptor. In Proceedings of the Berkeley Conference in Honor of Jerzy Neyman and Jack Keifer. Vol. 1. L. M. Le Cam and R. A. Olshen, eds, pp. 269–280. Wadsworth Publishing Co., Belmont, CA.

    Google Scholar 

  • Hamill, O.-P., Marty, A., Neher, E., Sakmann, B. and Sigworth, F.J. (1981) Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pfluegers Archive European Journal of Physiology, 391, 85–100.

    Google Scholar 

  • Hawkes, A. G., Jalali, A. and Colquhoun, D. (1990) The distributions of the apparent open times and shut times in a single channel record when brief events cannot be detected. Philosophical Transactions of the Royal Society of London A, 332, 511–538.

    Google Scholar 

  • Hawkes, A. G., Jalali, A. and Colquhoun, D. (1992) Asymptotic distributions of apparent open times and shut times in a single channel record allowing for the omission of brief events. Philosophical Transactions of the Royal Society of London B, 337, 383–404.

    Google Scholar 

  • Jalali, A. and Hawkes, A. G. (1992a) The distribution of apparent occupancy times in a two-state Markov process in which brief events cannot be detected. Advances in Applied Probability, 24, 288–301.

    Google Scholar 

  • Jalali, A. and Hawkes, A. G. (1992b) Generalised eigenproblems arising in aggregated Markov processes allowing for time interval omission. Advances in Applied Probability, 24, 302–321.

    Google Scholar 

  • Kelly, F. P. (1979) Reversibility and Stochastic Networks. Wiley, Chichester.

    Google Scholar 

  • Liebovitch, L. S., Fischbarg, J. and Koniarek, J. P. (1987) Ion channel kinetics: a model based on fractal scaling rather than multistate Markov processes. Mathematical Biosciences, 84, 37–68.

    Google Scholar 

  • Millhauser, G. L., Salpeter, E. E. and Oswald, R. E. (1988) Diffusion models of ion-channel gating and the origin of power-law distributions for single-channel recording. Proceedings of the National Academy of Sciences, USA, 85, 1503–1507.

    Google Scholar 

  • Milne, R. K., Yeo, G. F., Edeson, R. O. and Madsen, B. W. (1988) Stochastic modelling of a single ion channel: an alternating renewal approach with application to limited time resolution. Proceedings of the Royal Society of London, B, 233, 247–292.

    Google Scholar 

  • Milne, R. K., Yeo, G. F., Edeson, R. O. and Madsen, B. W. (1989) Estimation of single channel kinetic parameters from data subject to limited time resolution. Biophysical Journal, 55, 673–676.

    Google Scholar 

  • Pyke, R. (1961) Markov renewal processes: definitions and preliminary properties. Annals of Mathematical Statistics, 32, 1231–1242.

    Google Scholar 

  • Sakmann, B. and Neher, E. (eds) (1983) Single-Channel Recording. Plenum Press, New York.

    Google Scholar 

  • Yeo, G. F., Milne, R. K., Edeson, R. O. and Madsen, B. W. (1988) Statistical inference from single channel records: two-state Markov model with limited time resolution. Proceedings of the Royal Society of London B, 235, 63–94.

    Google Scholar 

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Ball, F.G., Yeo, G.F. Numerical evaluation of observed sojourn time distributions for a single ion channel incorporating time interval omission. Stat Comput 4, 1–12 (1994). https://doi.org/10.1007/BF00143919

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