Primary screen of a directed compound library against Nav1.5 channels using Population Patch Clamp technology
15 Oct 2008
Population Patch-Clamp™, introduced in 2005 by Molecular Devices, records ensemble averages from cells sealed onto 64 recording sites using a single amplifier per well. PPC reduces the variability inherent to conventional and single aperture planar patch-clamp techniques caused by a lack of exogenous channel expression, low seal resistances, and unstable recordings.
The use of PPC on Molecular Devices’ IonWorks Quattro™ instrument allows the acquisition of a data point from nearly 100% of the individual wells of the PatchPlate™ substrate, allowing the elimination of the quadruplicate addition requirement used with the IonWorks® HT system. Together, the increased data consistency and throughput provided by PPC make the IonWorks Quattro system suitable for directed screening of focused compound libraries. This application note describes a proof-of-concept study of 1564 compounds, demonstrating the use of IonWorks Quattro in a primary screen against the cardiac sodium channel, Nav1.5. The screen provides evidence that the throughput and robustness of this assay allows the screening of tens of thousands of compounds in a matter of weeks.