High throughput electrophysiology: new perspectives for ion channel drug discovery.
Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion channel targets accessible for drug screening. Specifically, genuine HTS parallel processing techniques based on arrays of planar silicon chips are being developed, but also lower throughput sequential techniques may be of value in compound screening, lead optimization, and safety screening. The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.
Willumsen
Niels J
NJ
Sophion Bioscience, Ballerup, Denmark. njw@sophion.dk
Bech
Morten
M
Olesen
Søren-Peter
SP
Jensen
Bo Skaaning
BS
Korsgaard
Mads P G
MP
Christophersen
Palle
P
D000818:Animals; D015195:Drug Design; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D018408:Patch-Clamp Techniques / Q000379:methods; D013997:Time Factors
D007473:Ion Channels