Emerging trends in ion channel-based assays for predicting the cardiac safety of drugs.
Regulators require prospective new drugs to be tested for potential cardiac effects that are relevant to drug safety. As a result, numerous technologies have been developed to screen drugs for off-target effects that compromise the function of hERG potassium channels, which are associated with acquired long QT syndrome - a disorder with a risk of sudden death as a result of arrhythmia. Automated patch clamp, which is the most important and commonly used technology for the preclinical assessment of the risk of arrhythmia, continues to evolve toward greater sophistication, higher success rates and increased ease of use. Patch clamp advances include the development of population patch clamp and the ability to make more consistent measurements from freshly thawed prevalidated cells. Nevertheless, several discrepancies between hERG testing, QT prolongation and the risk of arrhythmia have been well-publicized. As a result, ion channel screening has been further developed to enable the assaying of currents from a wider variety of cardiac ion channels and the measurement of action potentials from stem cell-derived cardiomyocyte-like cells. Emerging measurement technologies beyond patch clamp include the measurement of field potentials with multi-electrode arrays.
Witchel
Harry J
HJ
University of Sussex, Brighton and Sussex Medical School, Medical Research Building, Falmer, Brighton, BN1 9PS, UK. H.Witchel@bsms.ac.uk
D000818:Animals; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000187:drug effects / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C000606913:KCNH2 protein, human