Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels

  title={Fluctuations in the microsecond time range of the current through single acetylcholine receptor ion channels},
  author={David Colquhoun and Bert J. Sakmann},
Acetylcholine-like drugs cause ion channels in the skeletal muscle endplate to open briefly1, producing, at random intervals, rectangular pulses of current with constant amplitude but random duration, that can be recorded by the patch clamp method2,3. However, even when the agonist concentration is so low that channel activations are very well separated, we have observed, with high resolution methods4, that openings may be interrupted by shut periods (gaps) so brief that they are very unlikely… 
Rapid kinetics of single glutamate-receptor channels
It is found that glutamate-activated channels in locust muscle membrane show a large excess of both brief openings and closings over those expected from single exponential distributions, suggesting that a simple two-stage reaction scheme is sufficient to account for the observed kinetics.
Activation of ion channels in the frog endplate by several analogues of acetylcholine.
1. Single‐ion‐channel recording has been used to estimate the equilibrium concentration‐response relationship for several acetylcholine analogues. The response, corrected for desensitization, was
Single-channel and whole-cell currents evoked by acetylcholine in dissociated sympathetic neurons of the rat
Single acetylcholine-activated channels have been recorded from neurons dissociated from the sympathetic chain of 17–21 day old rats, and outward single-channel currents (of normal conductance) are detectable in isolated outside-out patches.
Dependence of acetylcholine receptor channel kinetics on agonist concentration in cultured mouse muscle fibres.
The two ligand binding sites are found to be very different in terms of their dissociation constants and their influence on the channel gating transitions, which have implications for the energetics of receptor activation and for the utilization of binding energy by the receptor.
Channel opening duration in adult muscle nAChRs determined by activated external ACh binding site
Transmembrane currents were recorded from single nAChR molecules, held at ACh or Epibatidine (Ebd) concentrations of 0.01, 0.1, 1, 10 or 100 µM and the measured current amplitudes had an absolutely fixed value of 15 pA.
Statistical properties of single sodium channels
Single channel currents were obtained from voltage-activated sodium channels in outside-out patches of tissue-cultured GH3 cells, a clonal line from rat pituitary gland, using 25 different time-homogeneous Markov chain models having up to five states using a maximum likelihood procedure to estimate the rate constants.
Fast events in single‐channel currents activated by acetylcholine and its analogues at the frog muscle end‐plate.
The fine structure of ion‐channel activations by junctional nicotinic receptors in adult frog muscle fibres has been investigated and the component of brief openings behaves, at low concentrations, as though it originates from openings of singly occupied channels.


Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist
From the temporal sequence of the pulses, derived estimates of the rates of activation and desensitization of the AChR-channel are derived and it is reported that in the presence of ACh concentrations sufficient to cause desensItization, single channel current pulses appear in groups.
Single-channel currents recorded from membrane of denervated frog muscle fibres
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.
Local anaesthetics transiently block currents through single acetylcholine‐receptor channels.
It is concluded that drug molecules reversibly block open end‐plate channels and that the flickering within a burst represents this fast, repeatedly occurring reaction.
On the stochastic properties of single ion channels
  • D. Colquhoun, A. Hawkes
  • Physics
    Proceedings of the Royal Society of London. Series B. Biological Sciences
  • 1981
It is desirable to be able to predict the appearance of currents that flow through single ion channels to enable interpretation of experiments in which single channel currents are observed, and to allow physical meaning to be attached to the results observed in kinetic experiments.
Decamethonium both opens and blocks endplate channels.
  • P. Adams, B. Sakmann
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1978
Three types of experiments revealed two kinetic processes controlling the opening of endplate channels, one that reflects agonist action and another that reflects local anesthetic-like blocking activity in decamethonium action.
Relaxation and fluctuations of membrane currents that flow through drug-operated channels
  • D. Colquhoun, A. Hawkes
  • Biology
    Proceedings of the Royal Society of London. Series B. Biological Sciences
  • 1977
The theoretical background is presented and 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 of drug action based on the law of mass action.
Voltage clamp analysis of acetylcholine produced end‐plate current fluctuations at frog neuromuscular junction
1. Acetylcholine produced end‐plate current (e.p.c.) noise is shown to be the results of statistical fluctuations in the ionic conductance of voltage clamped end‐plates of Rana pipiens.
The characteristics of ‘end‐plate noise’ produced by different depolarizing drugs
1. End‐plate depolarization and associated ‘membrane noise’ due to decamethonium, acetylthiocholine and suberyldicholine have been examined and compared with the effects of acetylcholine and