Key result
A wavelet-based method for designing fluctuating voltage inputs was developed and shown to maximize differences in computed ionic currents between various Markov models of Shaker K+ channels.
A novel wavelet-based algorithm for designing fluctuating voltage inputs can maximize differences in ionic current responses between competing Markov models, aiding in the refinement of ion channel gating models.
Supports K+ channel model refinement; leaves open validation in cardiac myocytes and clinical translation.
BACKGROUND: Fluctuation-induced phenomena caused by both random and deterministic stimuli have been previously studied in a variety of contexts. They are based on the interplay between the spectro-temporal patterns of the signal and the kinetics of the system it is applied to. The aim of this study was to develop a method for designing fluctuating inputs into nonlinear system which would elicit the most desired system output and to implement the method to studies of ion channels. RESULTS: We describe an algorithm based on constructing the input as a superposition of wavelets and optimizing it according to a selected cost functional. The algorithm is applied to ion channel electrophysiology where the input is the fluctuating voltage delivered through a patch-clamp experimental apparatus and the output is the whole-cell ionic current. The algorithm is optimized to aid selection of Markov models of the gating kinetics of the voltage-gated Shaker K+ channel and tested by comparison of numerically obtained ionic currents predicted by different models with experimental data obtained from the Shaker K+ channels. Other applications and optimization criteria are also suggested. CONCLUSION: The method described in this paper can be useful in development and testing of models of ion channel gating kinetics, developing voltage inputs that optimize certain nonequilibrium phenomena in ion channels, such as the kinetic focusing, and potentially has applications to other fields.
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Armin Kargol (2013) studied Ion channel electrophysiology (Shaker K+ channels). Wavelet-based fluctuating voltage protocols vs. Standard piecewise constant voltage protocols was evaluated on Difference in model responses (chi-square error between corresponding model currents). A wavelet-based method for designing fluctuating voltage inputs was developed and shown to maximize differences in computed ionic currents between various Markov models of Shaker K+ channels.
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