This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Related articles in Biophys. J. Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Colquhoun, D. Articles by Plested, A. J. R. Search for Related Content PubMed PubMed Citation Articles by Colquhoun, D. Articles by Plested, A. J. R.

How to Impose Microscopic Reversibility in Complex Reaction Mechanisms

David Colquhoun ^*, Kathryn A. Dowsland , Marco Beato ^* and Andrew J. R. Plested ^*

^* Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom; and Department of Computer Science, Nottingham University, and Gower Optimal Algorithms, Swansea SA3 4UH, United Kingdom

Correspondence: Address reprint requests to David Colquhoun, E-mail: d.colquhoun{at}ucl.ac.uk.

Most, but not all, ion channels appear to obey the law of microscopic reversibility (or detailed balance). During the fitting of reaction mechanisms it is therefore often required that cycles in the mechanism should obey microscopic reversibility at all times. In complex reaction mechanisms, especially those that contain cubic arrangements of states, it may not be obvious how to achieve this. Three general methods for imposing microscopic reversibility are described. The first method works by setting the ‘obvious’ four-state cycles in the correct order. The second method, based on the idea of a spanning tree, works by finding independent cycles (which will often have more than four states) such that the order in which they are set does not matter. The third method uses linear algebra to solve for constrained rates.

Related articles in Biophys. J.:

On Imposing Detailed Balance in Complex Reaction Mechanisms

Jin Yang, William J. Bruno, William S. Hlavacek, and John E. Pearson
Biophys. J. 2006 91: 1136-1141. [Full Text]  

This article has been cited by other articles:

				B. Roy, E. J. Halvey, and J. Garthwaite An Enzyme-linked Receptor Mechanism for Nitric Oxide-activated Guanylyl Cyclase J. Biol. Chem., July 4, 2008; 283(27): 18841 - 18851. [Abstract] [Full Text] [PDF]

				L. S. Milescu, T. Yamanishi, K. Ptak, M. Z. Mogri, and J. C. Smith Real-Time Kinetic Modeling of Voltage-Gated Ion Channels Using Dynamic Clamp Biophys. J., July 1, 2008; 95(1): 66 - 87. [Abstract] [Full Text] [PDF]

				M. Ederer and E. D. Gilles Thermodynamically Feasible Kinetic Models of Reaction Networks Biophys. J., March 15, 2007; 92(6): 1846 - 1857. [Abstract] [Full Text] [PDF]

				K. M. Kahlig, S. N. Misra, and A. L. George Jr Impaired Inactivation Gate Stabilization Predicts Increased Persistent Current for an Epilepsy-Associated SCN1A Mutation J. Neurosci., October 25, 2006; 26(43): 10958 - 10966. [Abstract] [Full Text] [PDF]

				J. Yang, W. J. Bruno, W. S. Hlavacek, and J. E. Pearson On Imposing Detailed Balance in Complex Reaction Mechanisms Biophys. J., August 1, 2006; 91(3): 1136 - 1141. [Full Text] [PDF]

				L. S. Milescu, G. Akk, and F. Sachs Maximum Likelihood Estimation of Ion Channel Kinetics from Macroscopic Currents Biophys. J., April 1, 2005; 88(4): 2494 - 2515. [Abstract] [Full Text] [PDF]

				V. Burzomato, M. Beato, P. J. Groot-Kormelink, D. Colquhoun, and L. G. Sivilotti Single-Channel Behavior of Heteromeric {alpha}1{beta} Glycine Receptors: An Attempt to Detect a Conformational Change before the Channel Opens J. Neurosci., December 1, 2004; 24(48): 10924 - 10940. [Abstract] [Full Text] [PDF]