Tue Dec 6 15:01:41 MET 1994 README.txt Author: Arnd Roth Abteilung Zellphysiologie Max-Planck-Institut fuer Medizinische Forschung Postfach 10 38 20, D-69028 Heidelberg, Germany roth@sunny.mpimf-heidelberg.mpg.de The Mathematica Packages in this directory implement parts of "Relaxation and fluctuations of membrane currents that flow through drug-operated channels" by D. Colquhoun & A.G. Hawkes, Proc. R. Soc. Lond. B 199, 231-262 (1977). Assuming a discrete state, continuous time Markov model for the behavior of ligand-gated ion channels, and given the transition rate constants between these states, the time evolution of their occupancy can be computed. This occupancy is then used to predict observables like the mean trans- membrane current and its coefficient of variation. "README.txt": this file. "DiagramToQMatrix.m" builds the Q-matrix from a transition diagram, prompting for nonzero transition rate constants. It automatically checks cyclic diagrams for microscopical reversibility. "ColquhounHawkes.m" contains various functions for - computing the occupancy of the different states of a channel using the Runge-Kutta algorithm, which allows for arbitrary transmitter concentration functions of time, - for plotting the mean current as a function of time, - its variance and third central moment, - and for computing the 20%/80% risetime of the current. "ColquhounHawkesMC.m" is an analog of "ColquhounHawkes.m" based on Monte Carlo simulation of the channel state transitions. It is restricted to square pulse transmitter concentration functions. Additionally, it contains a function that simulates experiments for determinimg the peak EPSC amplitude distribution for an ensemble of channels. This includes the effects of gaussian lowpass filtering and averaging over a certain interval of time during the peak. The most recent version of ColquhounHawkesMC, version 1.2, installs and uses some C routines collected in the file "chmc". This file is assumed to reside in the same directory as ColquhounHawkesMC, as specified in Appendix A of the manual. If this is not possible on certain computer systems, you can install "chmc" manually before you load the package. Alternatively, you might want to change the Package's Mathematica code portion that is responsible for installing the C routines. It is located directly below the definition of the error messages for the exported functions. For information on how to build "chmc" from "chmc.tm", please see Appendix B of the "Manual.ma" Notebook. The file "chmc.tm" has been updated to be MathLink compatible on Unix, Macintosh and Microsoft Windows. "NeuronInterface.m" provides two functions, WriteNeuronForm[] and WriteDoubleForm[]. They constitute an interface for transferring tabulated functions from Mathematica to Neuron and Double. Neuron is described in "A program for simulation of nerve equations with branching geometries" by M. Hines, Int. J. of Biomed. Computing 24, 55-68 (1989). For more information please see the manual Notebook, "Manual.ma". Further reading: 1) B. Hille, Ionic Channels of Excitable Membranes, 2nd ed., Sinauer, Sunderland, Mass., 1992. 2) B. Sakmann and E. Neher, Eds. Single-Channel Recording, Plenum, New York, 1983. 3) D. Johnston and S. M.-S. Wu, Foundations of Cellular Neurophysiology, MIT Press, Cambridge, Mass., 1995.