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A Multi-scale, Integrative Model of Cellular Electrophysiological Response Incorporating Intra/Extra-cellular Transport & Dynamics

J.J. Feng, S. Krishnamoorthy and S. Sundaram
CFD Research Corporation, US

Keywords:
multiscale model, ion channel, deconvolution of AP, simulation

Abstract:
Spurred by the growing confluence of nano and bio technologies, several novel micro/nano platforms (see for example, whole cell patch clamp devices [1]) are emerging for the high-throughput and/or high-fidelity study of the electrophysiological response of a single cell (or a few cells) to external excitation (potential, ion-induced depolarization or hormonal changes etc.). However, a significant challenge in interpreting the data from the instruments is the de-convolution of transport-related effects from pure electrophysiological phenomena, such as the gated responses. In response to this challenge, we have developed a novel multi-scale approach (Figure 1) in which, high-fidelity spatio-temporal models describing intra and extra cellular fluid motion and ion transport (e.g. representing calcium store dynamics) are coupled with an equivalent electric circuit network model describing ion-channel activation. In addition to a clear separation of the transport from the electrophysiology, and thereby more rigorous data analysis, the proposed model will also enable the knowledge-based design and development of novel patch-clamp experimental platforms.

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