http://www.ucl.ac.uk/Pharmacology/dc.htmlNews about single ion channel analysis and DC’s programs science.en-gb24 Feb 2006Copyright: (C) David Colquhounhttp://www.ucl.ac.uk/Pharmacology/dc.html15Remigijus Lape, David Colquhoun & Lucia Sivilotti (2008) Nature. 454, 722 – 728. This paper is the culmination of three years' work. For 50 years, ever since del Castillo & Katz (1957), it has been assumed that partial agonists will be deficient in producing the open-shut reaction. In this paper we find, for both glycine and nicotinic receptors, that opening and shutting of the channel is very much the same for partial and full agonists. The deficiency in partial agonists lies earlier, in the production of the pre-open 'flip' state (first identified in Burzomato et al 2004).http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#lcs-08http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#lcs-08Aug 2008pubsThe Schild method allows genuine physical equilibrium constants for competitive antagonists to be obtained from experiments in which complex responses are measured. This paper extends work done in 1973 (here), and gives conditions under which valid results can be obtained. The Schild method may still be valid with multiple agonist binding sites, even when agonist binding sites interact and/or are not identical. Trends in Pharmacological Sciences, 2007, 28, 608 – 614.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#schild07http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#schild07Dec 2007pubsWhat Have we Learned from Single Ion Channels?. This is invited perspective on Colquhoun & Sakmann (1985). Was our basic idea right? What have been the advances in thinking since them?http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#cp07http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#cp07May 2007pubsSingle channel study of the spasmodic mutation 1A52S in recombinant rat glycine receptors.When interpreted in terms of the 'flip' mechanism, the results suggest that the impairment of the receptor function results largely from a large reduction in the affinity of glycine for the flipped conformation,http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#ap07http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#ap07Mar 2007pubsThe subtitle was: "Some UK universities offer science degrees on complementary medicine. David Colquhoun argues that these are not science but anti-science, and asks who is too blame". This commentary piece caused something of a furore.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#nature07http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#nature07Mar 2007pubsA book review, of Nicotinic Acetylcholine Receptors by Jean-Pierre Changuex and Stuart J. Edelstein. (18 Feb 2007, Science). Verdict: “Nicotinic Acetylcholine Receptors is very good in parts. Nonetheless, as an overall view of the current state of our understanding, it is not only incomplete but sometimes positively misleading”.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#jpchttp://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#jpcMar 2007pubsUnderstanding Ion Channel Currents in Terms of Mechanisms. A course on analysis and interpretation of single ion channel records and macroscopic currents using matrix methods. Sign up now for 2007http://www.grad.ucl.ac.uk/courses/course-details.pht?course_ID=357http://www.grad.ucl.ac.uk/courses/course-details.pht?course_ID=357Feb 2006DCprogsReview in Nature of ‘How Numbers Reveal and Conceal the Truth’.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#numbershttp://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#numbersJuly 2006pubsI was asked to write about 'receptor theory', but I dislike that term because it sounds (and often is) divorced from experimental realities, and does not distinguish between physical and empirical descriptions. This history is about 8 or 10 people who have contributed the most to physical descriptions of receptors. It traces also the origins of ideas about competitive antagonists.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#tips06http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#tips06Feb 2006pubsOur flagship program for fitting reaction mechanisms to single ion channel observations has been improved by fixing a tricky numerical problem.http://www.ucl.ac.uk/Pharmacology/dcpr95.html#hjcfithttp://www.ucl.ac.uk/Pharmacology/dcpr95.html#hjcfitFeb 2006DCprogsFree programs for curve fitting, randomization tests, and especially for simulation and analysis of macroscopic and single ion channel experiments.http://www.ucl.ac.uk/Pharmacology/dcpr95.htmlhttp://www.ucl.ac.uk/Pharmacology/dcpr95.htmllDec 2004DCprogsBurzomato et al. 2004 suggest a mechanism for the gating of the glycine receptor. The mechanism is novel insofar as it seems to resolve an intermediate shut conformation between the resting and open conformations. It also provides an economical explanation for the apparent cooperativity of binding without having to postulate any interaction between distant binding sites.http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#vb-04http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#vb-04Dec 2004PapersSchorge and Colquhoun (2005) try to identify a mechanism for an NMDA receptor. This proved to be much harder than for the glycine receptor, but we find an opening rate for the channel that is much faster than that found by other labs, probably because our analysis methods can detect fast shut times (see Fig. 11).http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#ss05http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#ss05Dec 2005Papershttp://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#fun1http://www.ucl.ac.uk/Pharmacology/dc-bits/dcpubs.html#fun12006Papers