Untitled

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.

A Numerical Approach to Ion Channel Modelling Using Whole-Cell Voltage-Clamp Recordings and a Genetic Algorithm

“…The advantage of our scheme over the more commonly used gradient descent algorithms is that GAs do not require an initial guess of the parameters [12,34,35]. With a large enough dataset, it is possible to arrive at the global minimum even from a random starting point.…”

“…In contrast to the disjoint conventional method, the approach to data analysis and model fitting used here has been designated global curve fitting or the full-trace method [12,34]. However, the analysis presented here shows several important differences from previously suggested full-trace analyses.…”

“…For example, the classical Hodgkin-Huxley paradigm does not consider interactions between varying kinetic states, particularly that between activation and inactivation. This failure leads to an erroneous estimation of the kinetic parameters and thus of the predicted channel dynamics [12]. The best method, so far, for discovering the kinetics of ionic channels is by analysis of single-channel recordings [13].…”

A new methodology to define the equilibrium value function in the kinetics of (in)activation gates

“…Equations (7), (8) and (16) are also known as the Boltzmann relation [15]. They give sigmoid curves on a linear plot of m and h against V. Willms et al [17] noted that the Boltzmann curve in particular has proved to be adequate for describing the steady-state data from many currents. Our results also support that fact.…”

Neuronal ion-channel dynamics in silicon

“…3a) One flaw with linear thermodynamic models, and consequently with our circuit, is that the time constant decreases to extremely small values when either a ( V) and f (V) become large. One solution UH UpoLa-iaL)n This equates the minimum time constant at involves saturating the transition rates [9]. We realize this in our hyperpolarized and depolarized levels simplifying the expression to circuit by placing two additional transistors in series with the original Equation I 1 In addition, the bell-shape also requires Tmin to be two (Fig.…”