A-803467 Pharmacology Study on hNav1.8 and hNav1.7 Using the IonFluxTM System

It is well known that A-803467 potently blocks human Nav1.8 Na channels. The potency is selective for human Nav1.8 vs. human Nav1.2, Nav1.3, Nav1.5, and Nav1.7 by orders of magnitude (Jarvis & Krafte, 2007). Clinical studies have shown that Nav1.8 and Nav1.7 play a key role in neuropathic pain. They are highly sensitive to local anesthetic drugs, which makes them ideal targets for the development of pain relief drugs. In this application note, we describe the use of IonFlux, a novel microfluidic-based APC system, for recording Na current conducted by hNav1.7 and hNav1.8 channels expressed in HEK-293 cells, and pharmacology study of the A-803467 on both channels. The IonFlux system employs ensemble recording arrays consisting of 20 cells voltage clamped in parallel at 16 and 64 recording sites, each exposed to as many as eight different compounds or concentrations in a 96-well or 384-well format. The IonFlux instrument incorporates no internal robotics and offers rapid, microfluidic compound applications. It has a compact “plate reader” footprint suitable for bench-top operation.