An improved parameter estimation method for Hodgkin-Huxley models

We consider whole-cell voltage-clamp data of isolated currents characterize d by the Hodgkin-Huxley paradigm. We examine the errors associated with the typical parameter estimation method for these data and show them to be uns atisfactorally large especially if the time constants of activation and ina ctivation are not sufficiently separated. The size of these errors is due t o the fact that the steady-state and kinetic properties of the current are estimated disjointly. We present an improved parameter estimation method th at 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.