Cardiotoxicity drug screening based on whole-panel intracellular recording. Biosens Bioelectron 2022 Nov 15;216:114617
Date
08/27/2022Pubmed ID
36027802Pubmed Central ID
PMC9930661DOI
10.1016/j.bios.2022.114617Scopus ID
2-s2.0-85136501115 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
Unintended binding of small-molecule drugs to ion channels affects electrophysiological properties of cardiomyocytes and potentially leads to arrhythmia and heart failure. The waveforms of intracellular action potentials reflect the coordinated activities of cardiac ion channels and serve as a reliable means for assessing drug toxicity, but the implementation is limited by the low throughput of patch clamp for intracellular recording measurements. In the last decade, several new technologies are being developed to address this challenge. We recently developed the nanocrown electrode array (NcEA) technology that allows robust, parallel, and long-duration recording of intracellular action potentials (iAPs). Here, we demonstrate that NcEAs allow comparison of iAP waveforms before and after drug treatment from the same cell. This self-referencing comparison not only shows distinct drug effects of sodium, potassium, and calcium blockers, but also reveals subtle differences among three subclasses of sodium channel blockers with sub-millisecond accuracy. Furthermore, self-referencing comparison unveils heterogeneous drug responses among different cells. In our study, whole-panel simultaneous intracellular recording can be reliably achieved with ∼94% success rate. The average duration of intracellular recording is ∼30 min and some last longer than 2 h. With its high reliability, long recording duration, and easy-to-use nature, NcEA would be useful for iAP-based preclinical drug screening.
Author List
Yang Y, Liu A, Tsai CT, Liu C, Wu JC, Cui BAuthor
Chun Liu PhD Assistant Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Action PotentialsBiosensing Techniques
Calcium
Cardiotoxicity
Drug Evaluation, Preclinical
Humans
Ion Channels
Myocytes, Cardiac
Potassium
Reproducibility of Results
Sodium
Sodium Channel Blockers
