Estimation of ionic currents and compensation mechanisms from recursive piecewise assimilation of electrophysiological data

Abstract

The identification of ion channels expressed in neuronal function and neuronal dynamics is critical to understanding neurological disease. This program calls for advanced parameter estimation methods that infer ion channel properties from the electrical oscillations they induce across the cell membrane. Characterization of the expressed ion channels would allow detecting channelopathies and help devise more effective therapies for neurological and cardiac disease. Here, we describe Recursive Piecewise Data Assimilation (RPDA), as a computational method that successfully deconvolutes the ionic current waveforms of a hippocampal neuron from the assimilation of current-clamp recordings. The strength of this approach is to simultaneously estimate all ionic currents in the cell from a small but high-quality dataset. RPDA allows us to quantify collateral alterations in non-targeted ion channels that demonstrate the potential of the method as a drug toxicity counter-screen. The method is validated by estimating the selectivity and potency of known ion channel inhibitors in agreement with the standard pharmacological assay of inhibitor potency (IC50).