CiPA- "Identification of cardiac liability in drug discovery using the Port-a-Patch"
Port-a-Patch application note: (5.7 MB)
Cells were kindly provided by NEXEL and Charles River, USA.
In 2013 the Cardiac Safety Research Consortium (CSRC), the Health and Environmental Sciences Institute (HESI), and the US Food and Drug Administration (FDA) proposed a paradigm to improve assessment of the proarrhythmic risk of therapeutic compounds. This paradigm, the Comprehensive In-vitro Proarrhythmia Assay (CiPA), was introduced to provide a more complete assessment of proarrhythmic risk by evaluating and implementing currently available high throughput methods. An important part of this is the electrophysiological evaluation of hERG, and also other cardiac channels including NaV1.5 and CaV1.2. The Q&A draft from August 2020 describes how nonclinical assays such as patch clamp can be used as a part of an integrated risk assessment prior to first-in-human studies, and in later stages of clinical development.
Following up on hERG and NaV1.5 best practices and calibration standards which have been published recently on automated patch clamp devices, we show here cardiac ion channel recordings from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) or overexpressing cell lines generated with the world’s smallest patch clamp setups: Port-a-Patch and Port-a-Patch mini. Recordings at RT or physiological temperature of hERG recorded from HEK cells, and peak or late INa current recorded from iPSC-CMs or CHO cells are shown. INa-Late was activated by ATX-II and blocked by ranolazine, INa-Peak was blocked by tetracaine in a concentration-dependent manner, and hERG was blocked by increasing concentrations of dofetilide.