An Advanced Automated Patch Clamp Protocol Design to Investigate Drug-Ion Channel Binding Dynamics.

ABSTRACT: Standard high throughput screening projects using automated patch-clamp instruments often fail to grasp essential details of the mechanism of action, such as binding/unbinding dynamics and modulation of gating. In this study, we aim to demonstrate that depth of analysis can be combined with acceptable throughput on such instruments. Using the microfluidics-based automated patch clamp, IonFlux Mercury, we developed a method for a rapid assessment of the mechanism of action of sodium channel inhibitors, including their state-dependent association and dissociation kinetics. The method is based on a complex voltage protocol, which is repeated at 1 Hz. Using this time resolution we could monitor the onset and offset of both channel block and modulation of gating upon drug perfusion and washout.

SUBMITTER: Lukacs P 

PROVIDER: S-EPMC8513526 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature