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Full text of some older papers, including most theory papers

Older papers from DC lab  |   Some historical papers  |  

Some classical papers


Hill,A.V. (1909) The mode of action of nicotine and curari determined by the form of the contraction curve and the method of temperature coefficients. J. Physiol. (Lond), 39, 361-373.  [Get pdf (0.58 Mb)]
This is A.V. Hill's first paper. It describes the Langmuir equation (both rates and equilibrium) some time before Langmuir (1918) did so,

Haldane, J.B.S. (1930) Enzymes, Longmans, Green and Co.London.  [Get pdf (0.31.Mb)]
This is the section of Haldane's book that describes mechanisms: Michaelis-Menten and Briggs-Haldane, and in particular the case of competitive inhibition (see pp 46-47 of book, pp 20-21 of pdf file).

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Older papers from DC lab

The JSTOR web site now has in pdf format, in its General Science Collection, the entire contents of the Royal Society journals back to the 17th century, Proceedings of the National Academy of Sciences, and of Science. The pdf files can be downloaded by any site that subscribes to JSTOR.

Older papers from the Journal of Physiology are now available from the Pubmed central archive, For example

Colquhoun, D. & Sakmann, B. (1985). Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. Journal of Physiology ( London ) 369 , 501-557.
[Get pdf (7 Mb)]
See also the 'classical perspective on this paper, written in 2007 (here).

Colquhoun, D. & Hawkes, A.G. (1982) On the stochastic properties of bursts of single ion channel openings and of clusters of bursts. Philosophical Transactions of the Royal Society London B 300, 1-59.
This is the paper that describes the notation used in all subsequent papers, and uses it to obtain distributions of open and shut times, of burst properties, and the properties of clusters of bursts (it supersedes the 1981 paper)
[Get PDF (6 Mb!)]

Colquhoun, D., Dreyer, F., & Sheridan, R. E. (1979). The actions of tubocurarine at the frog neuromuscular junction. Journal of Physiology (London) 293, 247-284.
This paper describes the very long lasting channel blockages' that can be produced by (+)-tubocurarine (in addition to its competitive action). Such long blockages would be hard to identify on single channel records so even if we had been able to measure them in 1977 -78, the voltage-jump method used here might still have been the best.
[Get PDF (4.3 Mb)]

Colquhoun, D.(1981). How fast do drugs work?   Trends in Pharmacological Sciences 8, 212 – 217
This old paper is still sometimes found useful by students. It was written as an introduction to ideas about measuring the rates of reactions, as opposed to equilibrium constants. It therefore deals with macroscopic responses, noise analysis and single channels in an elementary way.
[Get pdf]

Colquhoun, D. & Hawkes, A. G. (1977). Relaxation and fluctuations of membrane currents that flow through drug-operated channels. Proceedings of the Royal Society London B 199, 231-262.  
[Get pdf 3,2 Mb]
This 1977 paper is the first of many papers written with Alan Hawkes. Its origin dates back to 1972 when I wrote Alan Hawkes to ask how the noise analysis, recently published by Katz & Miledi, could be generalised to any reaction mechanism. The theory predicted that the predominant time constant from noise analysis would be longer than the mean channel open time, for any realistic values of the rate constants. The physical meaning of this eluded us at first, but after being pressed by Bernard Katz to explain the result, we realised that it was a result of channel openings being predicted to not to occur singly, but in bursts. By the time the paper came out, Neher & Sakmann's 1976 paper had appeared and we were soon able to test the prediction,

Colquhoun, D.(1970). How long does a molecule stay on the receptor? Explanation of a paradox.   British Journal of Pharmacology 39, 215P
This is the abstract of a talk given at the 1969 meeting of the British Pharmacological Society. At the time I had just discovered, via Alan Hawkes, the waiting time paradox. This resolved, at a stroke, many of the problems that I'd been having in thinking about what happened at the level of a single drug-receptor complex.
[Get PDF]

Colquhoun, D. (1969). A comparison of estimators for a two-parameter hyperbola. Journal of Royal Statistical Society C 18, 130-140.
Another historical item: a study of the quality of estimates for a simple Langmuir equation by different methods of fitting, showing the best method is generally least squares.
[Get PDF (887 kb)]

Two older papers from books

These two papers have been scanned (because the books in which they appeared are now hard to find).

Colquhoun, D. (1973). The relation between classical and cooperative models for drug action. In Drug Receptors, ed. Rang, H. P., pp. 149-182. Macmillan Press, London.
[get pdf file: 4.04 Mb]
This paper attempted to reconcile the emerging knowledge of cooperativity in ion channel receptors with the more classical views. It showed that the Schild approach for competitive antagonsists was indeed valid for a wide range of receptor mechanisms, but that agonists could give results that were incompatible with Stephenson's ideas. But it failed to grasp completely the fatal error in the classical approach.

Colquhoun, D. (1987). Affinity, efficacy and receptor classification: is the classical theory still useful? In Perspectives on hormone receptor classification, ed. Black, J. W., pp. 103-114. Alan R. Liss Inc., New York.
[get pdf file: 2.35 Mb]
This paper explains why Stephenson's quantitative formulation contained an error, and how this error implied that none of the published methods for experimental determination of 'affinity' and 'efficacy' could actually achieve the separation of these quantities that had been claimed for them.

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The following are also available in pdf form (please email: d.colquhoun@ucl.ac.uk

Colquhoun, D. & Sheridan, R. E. (1981). The modes of action of gallamine. Proceedings of the Royal Society London B 211, 181-203.

Colquhoun, D. & Hawkes, A. G. (1981). On the stochastic properties of single ion channels. Proceedings of the Royal Society London B 211, 205-235.
(Note -this paper is superseded by the 1982 version (top of page)

Colquhoun, D. & Sakmann, B. (1985). Fast events in single-channel currents activated by acetylcholine and its analogues at the frog muscle end-plate. Journal of Physiology (London) 369, 501-557. [pdf available, but it is 36 Mb].

Ogden, D. C. & Colquhoun, D. (1985). Ion channel block by acetylcholine, carbachol and suberyldicholine at the frog neuromuscular junction. Proceedings of the Royal Society London B 225, 329-355.
[Get pdf]
This paper has two appendices of general interest. Appendix 1 gives algebraic reults for the area under a Lorentzian spectral density function that has been filtered with an 8-pole Butterworth filter. Appendix 2 uses the theory of clusters of bursts (C& H 1982) to analyse the effects of ion channel blockers that are not selective for the open state.

Mathie, A., Cull-Candy, S. G. & Colquhoun, D. (1987). Single-channel and whole cell currents evoked by acetylcholine in dissociated sympathetic neurons of the rat. Proceedings of the Royal Society London B 232, 239-248.

Colquhoun, D. & Hawkes, A. G. (1987). A note on correlations in single ion channel records. Proceedings of the Royal Society London B 230, 15-52.

Howe, J. R., Colquhoun, D. & Cull-Candy, S. G. (1988). On the kinetics of large-conductance glutamate-receptor ion channels in rat cerebellar granule neurons. Proceedings of the Royal Society London B 233, 407-422.

Colquhoun, D. and Ogden, D.C. (1988). Activation of ion channels in the frog end-plate by high concentrations of acetylcholine. Journal of Physiology, 395, 131-159.
[get pdf]

Hawkes, A. G., Jalali, A. & Colquhoun, D. (1990). The distributions of the apparent open times and shut times in a single channel record when brief events can not be detected. Philosophical Transactions of the Royal Society London A 332, 511-538. [Get PDF]

Colquhoun, D. & Hawkes, A. G. (1990). Stochastic properties of ion channel openings and bursts in a membrane patch that contains two channels: evidence concerning the number of channels present when a record containing only single openings is observed. Proceedings of the Royal Society London B 240, 453-477.

Gibb, A. J., Kojima, H., Carr, J. A. & Colquhoun, D. (1990). Expression of cloned receptor subunits produces multiple receptors. Proceedings of the Royal Society London B 242, 108-112.

Gibb, A. J. & Colquhoun, D. (1991). Glutamate activation of a single NMDA receptor-channel produces a cluster of channel openings. Proceedings of the Royal Society London B 243, 39-45.

Stern, P., Béhé, P., Schoepfer, R. & Colquhoun, D. (1992). Single channel properties of NMDA receptors expressed from cloned cDNAs: comparison with native receptors. Proceedings of the Royal Society London B 250, 271-277.

Edmonds, B. & Colquhoun, D. (1992). Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration. Proceedings of the Royal Society London B 250, 279-286.

Hawkes, A. G., Jalali, A. & 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 London B 337, 383-404. [Get PDF]

Béhé, P., Stern, P., Wyllie, D. J. A., Nassar, M., Schoepfer, R. & Colquhoun, D. (1995). Determination of the NMDA NR1 subunit copy number in recombinant NMDA receptors. Proceedings of the Royal Society London B 262, 205-213.

Colquhoun, D. & Hawkes, A. G. (1995). Desensitization of N-methyl-D-aspartate receptors: a problem of interpretation. Proceedings of the National Academy of Sciences, USA 92, 10327-10329.
Fredkin, D. R., Rice, J. A., Colquhoun, D. & Gibb, A. J. (1996). Persistence: a new statistic for characterizing ion-channel activity. Philosophical Transactions of the Royal Society London B 350, 353-367.

Colquhoun, D., Hawkes, A. G. & Srodzinski, K. (1996). Joint distributions of apparent open times and shut times of single ion channels and the maximum likelihood fitting of mechanisms. Philosophical Transactions of the Royal Society London A 354, 2555-2590.

Wyllie, D. J. A., Béhé, P., Nassar, M., Schoepfer, R. & Colquhoun, D. (1996). Single-channel currents from recombinant NMDA NR1a/NR2D receptors expressed in Xenopus oocytes. Proceedings of the Royal Society London B 263, 1079-1086.

Colquhoun, D., Hawkes, A. G., Merlushkin, A. & Edmonds, B. (1997). Properties of single ion channel currents elicited by a pulse of agonist concentration or voltage. Philosophical Transactions of the Royal Society London (Physical Sciences) A 355, 1743-1786.

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