Recording of nAChR α1 receptor currents using the IonFluxTM platform

Nicotinic acetylcholine receptors (nAChRs) are a class of pentameric ligand-gated ion channels involved in a wide variety of complex brain functions (memory, cognition, etc.) and neuromuscular transmission and plays a role in pathological conditions such as Alzheimer’s and Parkingson’s disease, schizophrenia and nicotine addiction. Additionally, nicotinic receptor agonists have potential as analgesics, anxiolytics and cognitive enhancers. The search for modulators of nAChR channels has been hampered by the lack of suitable high throughput electrophysiology platforms with the ability to interrogate fast desensitizing ligand gated channels.

In this report we present assay data, EC50, and recovery time scale measurements for the nACh receptor channel (α1) using the IonFlux electrophysiology platform. The IonFlux platform is a desktop instrument that utilizes microfluidic compound delivery on 100ms timescales, facilitating the recording of fast activating ligand gated ion channels (Fig. 1). A large number of cells (20 per ensemble) under voltage clamp can be exposed to a compound within a short time scale in parallel across the plate. Continuous recording, coupled with fast solution exchange, enables high throughput screening against ligand-gated ion channel targets.