Batch Action PoTential Analyser (BAPTA): an open source tool for automated high throughput analysis of cardiac action potentials

Abstract

The cardiac action potential (AP) is a key species-specific feature of cardiomyocytes that occurs in response to coordinated actions of ion channels. It represents the first step of the cardiac excitation-contraction coupling and it is crucial for cardiomyocyte (CM) physiology. Changes in the cardiac AP may primarily occur as a consequence of diseases or as a direct or unwanted response to drugs. Our ability to quantify these changes defines the reliability of our measurements and its throughput. Cardiac AP parameters are often quantified through manual time-consuming data analysis protocols or custom-made and proprietary data analysis pipelines; to the best of our knowledge, no tools are currently available for automated cardiac AP analysis and AP parameter quantification. Here we introduce a free and open source software tool named Batch Action PoTential Analyser (BAPTA), written in the R language, designed to i) overcome the inherent operator-dependent bias on trace selection affecting reproducibility, ii) vastly improve the throughput of the analyses of large datasets and iii) analyse both spontaneous and triggered APs from CMs of multiple species and origin. We present here four use-cases in which BAPTA can be used at high throughput to investigate the effects of: 1) a disease (cardiomyopathy) on rat CMs, 2) drugs on mouse pacemaker cells, 3) rate-dependency of AP duration in guinea pig CMs and 4) metabolic electrophysiological maturation in human stem-cell-derived CMs. Overall, BAPTA consistently provides faster, more reproducible and scalable readouts which excellently correlate with manual analyses performed by experienced electrophysiologists.