Abstract
Identification of drug induced electrical instability of the heart curtails development, and introduction, of potentially proarrhythmic drugs. This problem usually requires complimentary contact based approaches such as patch-clamp electrophysiology combined with field stimulation electrodes to observe and control the cell. This produces data with high signal to noise but requires direct physical contact generally preventing high-throughput, or prolonged, phenotyping of single cells or tissues. Combining genetically encoded optogenetic control and spectrally compatible calcium indicator tools into a single adenoviral vector allows the analogous capability for cell control with simultaneous cellular phenotyping without the need for contact. This combination can be applied to single rodent primary adult cardiomyocytes, and human stem cell derived cardiomyocytes, enabling contactless small molecule evaluation for inhibitors of sodium, potassium and calcium channels suggesting it may be useful for early toxicity work. In pancreatic beta-cells it reveals the effects of glucose and the KATP inhibitor gliclazide.
Highlights
Disrupting the ion channels responsible for depolarisation and repolarisation of cardiomyocytes by gene mutation or off-target drug effect increases the risk of sudden arrhythmic death [1]
Optical control and calcium imaging in primary adult cardiomyocytes not currently possible, changes to human stem cell derived cardiomyocyte (hSC-CM) differentiation and culture aspire to produce increasingly adult ventricular phenotypes, initial method development was undertaken in primary ventricular cardiomyocytes
This means that primary cardiomyocytes infected in vitro are often used towards the end of their natural life as time for gene expression is required with inevitable loss of quality
Summary
Disrupting the ion channels responsible for depolarisation and repolarisation of cardiomyocytes by gene mutation or off-target drug effect increases the risk of sudden arrhythmic death [1]. This pillar of safety pharmacology is principally studied using animal explant material and manual approaches requiring direct contact with the cell. Improvements to increase human relevance and experimental throughput are currently being evaluated in the Comprehensive. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
