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In recent years, human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) have found greater utility for in vitro studies as a physiologically relevant and widely available source of material. In particular, preparations of predominantly ventricular hiPSC-CMs have been used for cardiac safety liability assays such as the CiPA initiative. However, less work has been performed assessing pharmacological responses on atrial hiPSC-CMs, despite their known differences in ion channel expression.
Here, we show that commercially-available axoCells™ hiPSC-derived Atrial and Ventricular Cardiomyocytes show differential contractility responses when measured on the FLEXcyte 96 platform, including beat rate, beat duration and contractile force. Furthermore, chamber-specific responses were observed upon addition of specific classes of compounds such as GPCR agonists (acetylcholine and carbachol), a Ca2+ channel agonist (S-Bay K8644), an HCN channel antagonist (ivabradine) and K+ channel antagonists (4-AP and vernakalant). For example, Carbachol treatment produced marked effects on atrial cells, such as increased beat duration alongside a decrease in beat rate over time, but only minimal effects on ventricular cardiomyocytes.