POTASSIUM CHannels

IN SAFETY PHARMACOLOGY

Voltage-gated potassium channels, specially KV 11.1 (hERG), have long been the main target for cardiac safety pharmacology. hERG K+ channel inhibition by both cardiac and non-cardiac drugs have been identified as the most common cause of acquired, drug-induced LQTS (Long QT Syndrome) that may lead to sudden cardiac death. In fact, the side effect of hERG K+ channel inhibition is one of the major reasons of drug withdrawal or drug re-labeling. The gold standard of evaluating drug effects on hERG K+ current is manual patch clamp recording. However, this low-throughput, high-cost approach is limiting in safety screening of large numbers of drugs. Recently, automated electrophysiology systems have been developed that can obtain high-throughput recordings and achieve reasonably comparable results with manual patch clamp. However a major limitation started to appear in many HTS systems studying hERG and potassium channels in general is the lack of assay stability and longevity compared to manual patch clamp studies.

IonFlux Mercury complements manual patch clamp systems by delivering plate reader simplicity to complicated ion channel assays. IonFlux Mercury features include:

  • Continuously flowing solutions prolong assay stability

  • Short additions followed by controlled continuous wash of drugs allow calculation of binding kinetics

  • Precise temperature control allows physiological condition for drug interactions

Application Notes

Publications & Posters

Cell Line Receptor
HEK hERG
CHO hERG
hERG tail current affected by increasing voltage relationship

hERG tail current affected by increasing voltage relationship

Longevity of hERG recording and two types of compound application sequences. Experimental screen capture showing two cumulative blocker concentration sequences, followed by a protocol during which the blocker is removed before each subsequent concentration is applied.

Longevity of hERG recording and two types of compound application sequences. Experimental screen capture showing two cumulative blocker concentration sequences, followed by a protocol during which the blocker is removed before each subsequent concentration is applied.