Abstract
We consider whole-cell voltage-clamp data of isolated currents characterized by the Hodgkin-Huxley paradigm. We examine the errors associated with the typical parameter estimation method for these data and show them to be unsatisfactorally large especially if the time constants of activation and inactivation are not sufficiently separated. The size of these errors is due to the fact that the steady-state and kinetic properties of the current are estimated disjointly. We present an improved parameter estimation method that utilizes all of the information in the voltage-clamp conductance data to estimate steady-state and kinetic properties simultaneously and illustrate its success compared to the standard method using simulated data and data from P. interruptus shal channels expressed in oocytes.
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Baro DJ, Coniglio LM, Cole CL, Rodriguez HE, Lubell JK, Kim MT, Harris-Warrick RM (1996) Lobster shal: Comparison with Drosophila shal and native potassium currents in identified neurons. J. Neurosci. 16:1689–1701.
Baro DJ, Levini RM, Kim MT, Willms AR, Cole CL, Rodriguez HE, Harris-Warrick RM (1997) Quantitative single-cell-reverse transcription–PCR demonstrates that A-current magnitude varies as a linear function of shal gene expression in identified stomatogastric neurons. J. Neurosci. 17:6597–6610.
Buchholtz F, Golowasch J, Epstein IR, Marder E (1992) Mathematical model of an identified stomatogastric ganglion neuron. J. Neurophysiol. 67:332–340.
Filatov GN, Nguyen TP, Kraner SD, Barchi RL (1998) Inactivation and secondary structure in the D4/S4-5 region of the SkM1 sodium channel. J. Gen. Physiol. 111:703–715.
Golowasch J, Buchholtz F, Epstein IR, Marder E (1992) Contribution of individual ionic currents to activity of a model stomatogastric ganglion neuron. J. Neurophysiol. 67:341–349.
Golowasch J, Marder E (1992) Ionic currents of the lateral pyloric neuron of the stomatogastric ganglion of the crab. J. Neurophysiol. 67:318–331.
Harris-Warrick RM, Coniglio LM, Barazangi N, Guckenheimer J, Gueron S (1995) Dopamine modulation of transient potassium current evokes phase shifts in a central pattern generator network. J. Neurosci. 15:342–358.
Harris-Warrick RM, Coniglio LM, Levini RM, Gueron S, Guckenheimer J (1995) Dopamine modulation of two subthreshold currents produces phase shifts in activity of an identified motoneuron. J. Neurophysiol. 74:1404–1420.
Hille B (1992) Ionic Channels of Excitable Membranes. Sinauer, Sunderland, MA.
Hodgkin AL, Huxley AF (1952a) The dual effect of membrane potential on sodium conductance in the giant axon of Loligo. J. Physiol. Lond. 116:497–506.
Hodgkin AL, Huxley AF (1952b) Aquantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. Lond. 117:500–544.
Jerng HH, Covarrubias M (1997) K+ channel inactivation mediated by concerted action of the cytoplasmic N-and C-terminal domains. Biophys. J. 72:163–174.
Johnston D, Wu SM (1995) Foundations of Cellular Neurophysiology. MIT Press, Cambridge, MA.
Press WH, Flannery BP, Teukolsky SA, Vetterling WT (1988) Numerical Recipes in Fortran: The Art of Scientific Computing. Cambridge University Press, Cambridge, MA.
Wei A, Covarrubias M, Butler A, Baker K, Pak M, Salkoff L (1990) K+ current diversity is produced by an extended gene family conserved in Drosophila and mouse. Science 248:599–603.
Willms AR (1997) Hodgkin-Huxley Models: Parameter Estimation Issues, an Application to Spike Frequency Adaptation, and Analysis of a Subcritical Hopf-Homoclinic Bifurcation. Ph.D. thesis, Cornell University.
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Willms, A.R., Baro, D.J., Harris-Warrick, R.M. et al. An Improved Parameter Estimation Method for Hodgkin-Huxley Models. J Comput Neurosci 6, 145–168 (1999). https://doi.org/10.1023/A:1008880518515
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DOI: https://doi.org/10.1023/A:1008880518515