title: Analysis of real-time numerical integration methods applied to dynamic clamp experiments.
abstract: Real-time systems are frequently used as an experimental tool, whereby simulated models interact in real time with neurophysiological experiments. The most demanding of these techniques is known as the dynamic clamp, where simulated ion channel conductances are artificially injected into a neuron via intracellular electrodes for measurement and stimulation. Methodologies for implementing the numerical integration of the gating variables in real time typically employ first-order numerical methods, either Euler or exponential Euler (EE). EE is often used for rapidly integrating ion channel gating variables. We find via simulation studies that for small time steps, both methods are comparable, but at larger time steps, EE performs worse than Euler. We derive error bounds for both methods, and find that the error can be characterized in terms of two ratios: time step over time constant, and voltage measurement error over the slope factor of the steady-state activation curve of the voltage-dependent gating variable. These ratios reliably bound the simulation error and yield results consistent with the simulation analysis. Our bounds quantitatively illustrate how measurement error restricts the accuracy that can be obtained by using smaller step sizes. Finally, we demonstrate that Euler can be computed with identical computational efficiency as EE.
authors.affiliation: Laboratory for Neuroengineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, USA. r.butera@ece.gatech.edu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Butera
authors.forename: Maeve L
authors.initials: ML
authors.lastname: McCarthy
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D003198:Computer Simulation; D003199:Computer Systems; D005246:Feedback / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008959:Models, Neurological; D009716:Numerical Analysis, Computer-Assisted; D018408:Patch-Clamp Techniques / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D007473:Ion Channels