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2015 - High Throughput Automated Patch Clamp of Ion Channels Important in Cardiac Safety and Drug Discovery

icon sp96  SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) poster, Chantest Meeting 2015   logo pdf   (1.9 MB)

 Abstract:

One important part of the drug discovery process is the early assessment of a drug’s safety profile. The new paradigm in cardiac drug safety screening, the Comprehensive In-vitro Proarrhythmia Assay (CiPA) initiative, is being introduced to provide a more complete assessment of proarrythmic risk by evaluating and implementing currently available high throughput methods. An important part of this is an extension of the electrophysiological evaluation of ion channels beyond hERG to include other cardiac channels such as NaV1.5, CaV1.2, KVLQT1 (KV7.1) and Kir2.1. The ion channel CaV1.2, however, is not only found in cardiac tissue but also in the CNS and smooth muscle cells, amongst others. It is thought to play a role in CNS function, cardiac and smooth muscle contraction, neuroendocrine regulation and a multitude of other processes (Hofmann, Flockerzi, Kahl, & Wegener, 2014). Blockers of CaV1.2 are used for the treatment of hypertension and angina and pharmacology of two such compounds (verapamil and nifedipine) are shown here. In this study, HEK or CHO cells expressing the ion channels hERG, NaV1.5, CaV1.2, KVLQT1 (KV7.1), KV4.3 and Kir2.1 were recorded simultaneously on an automated patch clamp instrument recording from 384 cells in parallel. Additionally, CHO cells expressing CaV1.2 were recorded using multi-hole chips and pharmacology of verapamil and nifedipine will be shown.

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