The cardiac late Na+ current (late INa) generates persistent inward currents throughout the plateau phase of the ventricular action potential and is an important determinant of repolarisation rate, EADs and arrythmia risk. As inhibition of late INa can offset drug effects on hERG and other repolarising K+ conductances it is one of the key cardiac channels in the Comprehensive in vitro Proarrythmia Assay CiPA panel being developed by the FDA to improve human clinical arrythmia risk assessment.
The HESI Cardiac Safety Committee present results from an international ion channel research study that assessed the variability of hERG data generated using automated patch clamp platforms (QPatch 48, Qube 384 and the SyncroPatch 384i) across four different labs.
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).