Simultaneous assessment of compound activity on cardiac Nav1.5 peak and late currents in an automated patch clamp platform

High throughput in vitro profiling of the cardiac Na_V1.5 peak sodium current (I_Na) is widely used in cardiac safety screening. However, there is no standardized high throughput method to measure late I_Na. This study assessed the pharmacological and biophysical properties of veratridine and ATX-II, as well as the channel mutation (Na_V1.5-∆KPQ) on the late I_Na. We describe a method for simultaneous measurement of both peak and late I_Na.