High-throughput methods for cardiac cellular electrophysiology studies: the road to personalized medicine

Abstract

Personalized medicine refers to the tailored application of medical treatment at an individual level, taking into account the specific genotype or phenotype of each patient for targeted therapy. In the context of cardiovascular diseases, implementing personalized medicine is challenging due to the high costs involved and the slow pace of identifying the pathogenicity of genetic variants, deciphering molecular mechanisms of disease and testing treatment approaches. Scalable cellular models such as human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) serve as useful in vitro tools which reflect individual patient genetics and retain clinical phenotypes. High throughput functional assessment of these constructs is necessary to rapidly assess cardiac pathogenicity and test new therapeutics if personalized medicine is to become a reality. High throughput photometry recordings of single cells coupled with potentiometric probes offer cost effective alternatives to traditional patch-clamp assessments of cardiomyocyte action potential characteristics. Importantly, automated patch-clamp (APC) is rapidly emerging in the pharmaceutical industry and academia as a powerful method to assess individual membrane-bound ionic currents and ion channel biophysics over multiple cells in parallel. Now amenable to primary cell and hiPSC-CM measurement, APC represents an exciting leap forward in the characterization of a multitude of molecular mechanisms that underlie clinical cardiac phenotypes. This review provides a summary of state-of-the-art high throughput electrophysiological techniques to assess cardiac electrophysiology and an overview of recent works which successfully integrate these methods into basic science research which could potentially facilitate future implementation of personalized medicine at a clinical level.

Special Issue: “Recent Advances in Ion Channels and Ion Channelopathies”

“…The traditional electrophysiological methods, however, require analysis of mutations individually which results in very low throughput. Recent research in this space has led to the development of high-throughput sequencing and proteomics techniques, which allow for detailed analysis of disease-relevant molecular mutations in ion channels [9], which may improve diagnosis of ion channelopathies associated with genetic mutations.…”