Aims and Objectives: 

Embryonic stem (ES) and induced pluripotent stem (iPS) cells are attractive sources for ex vivo generation of cardiomyocytes. These systems are well-suited for developmental studies, high throughput drug screenings and cell replacement approaches. In our previous work we demonstrated that activation of calcium-activated potassium channels (SKCas) leads to an induction of mesodermal differentiation and an enrichment of cardiac pacemaker cells from ES cells. It is obvious that this could be a powerful approach for clinical applications. However, prior to that several biological obstacles have to be overcome. We have addressed critical issues in the present manuscript focusing on (i) serum-free differentiation, (ii) avoidance of embryoid body formation, and (iii) implementation of this strategy in iPS cells.

Methods and Results: 

The first two points have been solved in an ES cell-based assay, while the latter issue was addressed by a systematic evaluation of SKCa function in a set of distinctly generated iPS cell lines.

Conclusion: 

Our data overcome several limitations for clinical applications. We substantiate the feasibility of our cardiac subtype specifying protocols for iPS cells and would like to stress that optimization of the protocols for iPS cells is critical due to their relevance as an autologous cell source.