Ion channels are membrane proteins that regulate the entrance and departure of specific ions from cells, thus influencing the physiology of all cells. These ion flows also underlie electrical impulses required for sensory and motor functions of the brain, control of contraction of heart, skeletal, smooth and vascular muscle, as well as nutrient uptake, hormone secretion, cell replication and foetal development.

The extensive amount of knowledge accumulated over the last few years on the physiological importance of ion channels and, consequently, the broad expectation that drugs which modify the activity of these proteins could have therapeutic benefit, has triggered resurgence in the study of ion channels in both academic and pharmaceutical institutions.

Advances in assay technology are driving an exciting new era in ion channel drug discovery. Here, we present a case study describing the use of computational chemistry and focussed library screening to drive rapid hit identification.

Ion channels are membrane spanning proteins with narrow hydrophilic pores that support the passive flux of inorganic ions across the cell membrane.

The advent of higher throughput patch clamp electrophysiology systems has begun to change the face of ion channel drug discovery. Systems such as IonWorksHT, PatchXpress and QPatch should allow electrophysiology to be re-positioned from an occasional reagent and compound ‘spot-check’ method, to a frontline gene expression analysis tool and drug screening workhorse. This article chronicles the evolution of these systems, their technical capabilities and impact on drug discovery.