IonWorks Barracuda Assay for Assessment of State-Dependent Sodium Channel Modulators.

Voltage-gated sodium channels represent important drug targets. The implementation of higher throughput electrophysiology assays is necessary to characterize the interaction of test compounds with several conformational states of the channel, but has presented significant challenges. We describe a novel high throughput approach to assess the effects of test agents on voltage-gated sodium currents. The multiple protocol mode of the automated electrophysiology instrument IonWorks Barracuda was used to control the level of inactivation and monitor current stability. Good temporal stability of currents and spatial uniformity of inactivation were obtained by optimizing the experimental conditions. The resulting assay allowed for robust assessment of state-dependent effects of test agents and enabled direct comparison of compound potency across several sodium channel subtypes at equivalent levels of inactivation.