Relaxation and fluctuations of membrane currents that flow through drug-operated channels

@article{Colquhoun1977RelaxationAF,
  title={Relaxation and fluctuations of membrane currents that flow through drug-operated channels},
  author={David Colquhoun and Alan G. Hawkes},
  journal={Proceedings of the Royal Society of London. Series B. Biological Sciences},
  year={1977},
  volume={199},
  pages={231 - 262}
}
  • D. Colquhoun, A. Hawkes
  • Published 14 November 1977
  • Biology
  • Proceedings of the Royal Society of London. Series B. Biological Sciences
The theoretical background is presented for (a) the relaxation towards equilibrium of drug-induced membrane currents, and (b) the fluctuations of membrane current about its equilibrium value that originate in the opening and closing of membrane ion channels. General expressions are given that relate the relaxation current, autocovariance function, spectral density function, fluctuation variance and mean open channel lifetime to the rate constants and single channel conductances for any theory… 
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References

SHOWING 1-10 OF 54 REFERENCES
Voltage-dependence of drug-induced conductance in frog neuromuscular junction.
  • E. Neher, B. Sakmann
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1975
TLDR
Membrane currents from voltage-clamped frog muscle fibers were recorded during iontophoretic application of steady doses of carbachol, acetylcholine, and suberyldicholine to the endplate region and the time constant of relaxation was found to be voltage-dependent.
Single-channel currents recorded from membrane of denervated frog muscle fibres
TLDR
A more sensitive method of conductance measurement is reported, which, in appropriate conditions, reveals discrete changes in conductance that show many of the features that have been postulated for single ionic channels.
Relaxation measurements on the acetylcholine receptor.
  • R. Sheridan, H. Lester
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1975
TLDR
The kinetic data explain several aspects of the steady-state conductance induced by agonists, but shed no light on apparent cooperative effects.
Noise analysis of drug induced voltage clamp currents in denervated frog muscle fibres.
TLDR
The autocorrelation function of drug‐induced current fluctuations, recorded at the former end‐plate region of chronically denervated fibres often shows both a fast and a slow time constant, which could indicate that two populations of channels exist at theFormer end‐ plate region ofDenervated muscle fibres.
Conductance of channels opened by acetylcholine-like drugs in muscle end-plate
TLDR
This work has estimated average single channel conductances for four cholinomimetic agonists, and finds this prediction that a channel, once it is open, will have the same conductance whichever drug caused it to open is not confirmed.
Fluctuations and noise in kinetic systems. Application to K+ channels in the squid axon.
Inferences about membrane properties from electrical noise measurements.
A quantitative description of membrane current and its application to conduction and excitation in nerve.
TLDR
This article concludes a series of papers concerned with the flow of electric current through the surface membrane of a giant nerve fibre by putting them into mathematical form and showing that they will account for conduction and excitation in quantitative terms.
Conductance increases produced by bath application of cholinergic agonists to Electrophorus electroplaques
When solutions containing agonists are applied to the innervated face of an Electrophorus electroplaque, the membrane's conductance increases. The agonist-induced conductance is increased at more…
The effect of procaine on the action of acetylcholine at the neuromuscular junction.
TLDR
The average time course of the ACh shot effects is discussed in terms of alternative hypotheses, one attributing the complex shape to each elementary event, the other involving sequential reaction steps which produce two unequal populations of ion gates of different “life‐times”.
...
...