Observations on conducting whole-cell patch clamping of the hERG cardiac K+channel in pure human serum
| Autor: | Michelle Searles, David Rampe, Jiesheng Kang, Yongyi Luo |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug congenital hereditary and neonatal diseases and abnormalities biology business.industry media_common.quotation_subject hERG Plasma protein binding Pharmacology Toxicology 030226 pharmacology & pharmacy QT interval 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Pharmacodynamics biology.protein Medicine Terfenadine cardiovascular diseases Patch clamp business IC50 medicine.drug media_common |
| Zdroj: | Journal of Applied Toxicology. 37:445-453 |
| ISSN: | 0260-437X |
| DOI: | 10.1002/jat.3377 |
| Popis: | Inhibition of the human ether-a-go-go-related gene (hERG) K+ channel by drugs leads to QT prolongation on the electrocardiogram and can result in serious cardiac arrhythmia. For this reason, screening of drugs on hERG is mandatory during the drug development process. Patch clamp electrophysiology in a defined physiological saline solution (PSS) represents the standard method for assaying drug effects on the channel. To make the assay more translatable to clinical studies, we have conducted whole-cell patch clamping of hERG using pure human serum as the extracellular medium. Pure human serum had little effect on the hERG channel waveform or the current-voltage relationship when compared to PSS. hERG current recordings were highly stable in serum at room temperature, but prolonged recordings at the physiological temperature required prior heat inactivation of the serum. Compared to PSS, the IC50 values, conducted at room temperature, of the classic hERG blocking drugs cisapride, moxifloxacin, and terfenadine were shifted to the right by an extent predicted by their known plasma protein binding, but we did not detect any differences in IC50 s between male and female serum. Total plasma levels of these drugs associated with clinical QT prolongation corresponded to small ( |
| Databáze: | OpenAIRE |
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