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
multiscale model, ion channel, deconvolution of AP, simulation
Spurred by the growing confluence of nano and bio technologies, several novel micro/nano platforms (see for example, whole cell patch clamp devices ) 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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Nanotech 2005 Conference Program Abstract