Estimating neuronal conductance model parameters using dynamic action potential clamp.

BACKGROUND: Parameterization of neuronal membrane conductance models relies on data acquired from current clamp (CC) or voltage clamp (VC) recordings. Although the CC approach provides key information on a neuron's firing properties, it is often difficult to disentangle the influence of multiple conductances that contribute to the excitation properties of a real neuron. Isolation of a single conductance using pharmacological agents or heterologous expression simplifies analysis but requires extensive VC evaluation to explore the complete state behavior of the channel of interest. NEW METHOD: We present an improved parameterization approach that uses data derived from dynamic action potential clamp (DAPC) recordings to extract conductance equation parameters. We demonstrate the utility of the approach by applying it to the standard Hodgkin-Huxley conductance model although other conductance models could be easily incorporated as well. RESULTS: Using a fully simulated setup we show that, with as few as five action potentials previously recorded in DAPC mode, sodium conductance equation parameters can be determined with average parameter errors of less than 4% while action potential firing accuracy approaches 100%. In real DAPC experiments, we show that by "training" our model with five or fewer action potentials, subsequent firing lasting for several seconds could be predicted with ˜96% mean firing rate accuracy and 94% temporal overlap accuracy. COMPARISON WITH EXISTING METHODS: Our DAPC-based approach surpasses the accuracy of VC-based approaches for extracting conductance equation parameters with a significantly reduced temporal overhead. CONCLUSION: DAPC-based approach will facilitate the rapid and systematic characterization of neuronal channelopathies.