New bioassays could cut drug screening times. Researchers at GlaxoSmithKline in the UK and US have demonstrated how a technique called population patch clamp (PPC) electrophysiology can be used to probe multiple drug targets simultaneously.

Ion channels are pores that transport ions across cell membranes and are the molecular target of a number of drugs. Electrophysiology involves recording electrical currents across a cell membrane and, since these change when an ion channel responds to a drug, the method can be successful in drug screening. 

Single-cell patch clamp electrophysiology is seen as the gold standard for monitoring these drug-ion channel interactions as it provides highly reliable information; however, it is too slow to be used as a primary screening method. The PPC approach measures the current across several cells in a single well, with multiple wells being analysed at the same time. This generates lower quality data but in a high-throughput format, allowing rapid screening of candidate drug libraries.

Now, Derek Trezise at GlaxoSmithKline's site in Harlow, UK, and co-workers have used the PPC method in assay duplexing, where two different assays are run at the same time. This allows, for instance, one drug to be tested against two different cellular targets. The approach further increases the rate at which potential drugs can be analysed, cutting screening times and costs. 'Potentially there is scope for even higher throughput,' said Derek Trezise, adding that, on the technical side, 'the challenge is to improve the fluidics.'    

The team was also able to measure modulator assays. These record a drug's effect on ion channels that require an activator, such as an additional ion. Being able to use PPC in this way extends the scope of the method.

'Population patch clamp provides a new approach with real promise to improve the efficiency of generating high-information-content activity data for ion channel targets,' said Jesús González, an expert in ion channel drug discovery from Vertex Pharmaceuticals, San Diego, US. 'Assaying simultaneously from a population of cells should improve in vitro pharmacological analysis and profiling of some challenging ion channel targets,' he added.

Russell Johnson