**6. Limitations**

We are aware that the description of the BKCa in a single control cell line of hiPSC-CMs is of limited transferability, especially since we could not uncover conditions or mechanisms of the unexpected BKCa expression. Nevertheless, presence of BKCa is a good example that hiPSC-CMs can express non-cardiac proteins with a huge impact on physiological parameters. Although IBTX has been described as selective for IBK,Ca [41], non-specific effects of IBTX cannot be completely excluded. LV tissue was obtained from patients with heart disease; a potential difference to healthy LV tissue is unclear. We implemented the BK in the previously developed hiPSC-CM model [5], but we failed to induce notch/oscillations in that model. Obviously, our present model does not reflect the cellular ultrastructure at the level of detail that would be required for simulating the putative close proximity of the BK and CaL channels.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2073-4409/9/1/253/s1; Figure S1: Outward currents in iCell human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the effect of iberiotoxin (IBTX) and Figure S2: Cardiomyocyte content analyzed by flow cytometry. Figure S3: Karyotype of hiPS-cells. Figure S4: RNA sequencing of BK related genes in hiPSC-CMs. Figure S5: Immunoflurorescence analysis of BK in hiPSC-CMs.

**Author Contributions:** Conceptualization, A.H. (András Horváth), T.C. and M.D.L.; methodology, A.H. (András Horváth), T.C. and M.D.L.; software, J.T.K., M.S.; validation, T.C. and M.D.L.; formal analysis, M.D.L.; investigation, A.H. (András Horváth), M.P., M.S. and M.D.L.; resources, M.P., A.T.L.Z., M.S., U.S., I.M., B.U. and E.G.; data curation, T.C. and M.D.L.; writing—original draft preparation, T.C. and M.D.L.; writing—review and editing, A.H. (András Horváth), T.C., J.T.K., M.P., A.T.L.Z., I.M., B.U., C.M., E.G., A.H. (Arne Hansen), T.E. and M.D.L.; visualization, T.C. and M.D.L.; supervision, T.C., T.E. and M.D.L.; funding acquisition, T.C., A.H. (Arne Hansen), J.T.K., C.M., T.E. and M.D.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was supported by the German Centre for Cardiovascular Research (DZHK) and the German Ministry of Research Education (BMBF) to M.D.L. & A.H. (Arne Hansen), the German Research Foundation (DFG, 3423/5-1) to A.H. (Arne Hansen), the European Research Council Advanced Grant (IndivuHeart, 340248) to T.E., the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant (AFib-TrainNet, 675351) to T.E. and T.C.; the Research Promotion Fund of the Faculty of Medicine (Hamburg) to M.P. and M.D.L. ("Clinician Scientist Program" and "Project funding for young scientists"), the Pirkanmaa Regional Fund of the Finnish Cultural Foundation and the Academy of Finland Centre of Excellence in Body-on-Chip Research to J.T.K.

**Acknowledgments:** The authors thank Alessandra Moretti and Dennis Schade for their kind contribution of materials. The authors gratefully acknowledge expert technical advice and help in providing hiPSC-CMs and EHTs from Anika Knaust, Tessa Werner, Mirja L. Schulze, Marta Lemme, Anna Steenpass, Thomas Schulze, Birgit Klampe, Lisa Krämer, Aya Domke-Shibamiya and Sandra Laufer. FACS analyses were performed at the UKE FACS Sorting Core Unit.

**Conflicts of Interest:** I.M., A.H. (Arne Hansen) and T.E. are cofounder of EHT Technologies GmbH, Hamburg.

### **Abbreviations**

