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Fast Determination of Macroscopic Ion Channel Time Constants As a Metric Orthogonal to Standard Activity Measurements in Ion Channel Screening

Ion Channel Retreat, Vancouver, BC, Canada
June 25, 2014

This poster illustrates the utility and importance of a metric for ion channel modulation by compounds that is orthogonal to the commonly used percent activity calculated e.g. from peak current vs. control. In this example, we determine the (macroscopic) time constant (tau) of channel inactivation. In order to achieve a very fast analysis of results concomitant with routine high-throughput screening, we calculate tau by exponential decay functions. A recently developed APC assay on the IonFlux HT platform, using a HEK hNav1.7 cell line, serves as a benchmark for this approach. We first show results illustrating the rationale of this method using a known modulator of hNav1.7 inactivation, measured on the IonFlux instrument. We then outline a workflow based on Genedata Screener®, enabling an almost real-time, interactive generation of high-quality results for the several thousands of compounds tested. Combining the APC assay with the Genedata Screener workflow, we illustrate how screening campaigns will benefit from exploiting additional information from time-resolved APC measurements in real time, enabling recovery of potentially missed false-negatives and providing additional guidance for hit selection.

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