Calcium-Activated Potassium Channels, Cardiogenesis of Pluripotent Stem Cells, and Enrichment of Pacemaker-Like Cells

Potassium channels represent the largest group of pore proteins regulating K+efflux from the K+-rich inner cell to the extracellular compartment, thereby inducing changes in the membrane potential. Activity is regulated either by voltage or calcium concentrations, thus the nomenclature of voltage- and calcium-activated potassium channels. The critical role of potassium ion channels in developmental processes remains enigmatic, although it is well accepted that cell differentiation and maturation affect the expression patterns of certain ion channels. Recently, a series of studies delineated the precise function of calcium-activated potassium channels during cardiac, particularly pacemaker, cell development using human and mouse pluripotent stem cell models. It has become evident that this protein family not only regulates proliferation, apoptosis, and cell metabolism but also drives critical events during organ development such as the heart. This review summarizes the literature on calcium-activated potassium channels, their role in cardiac stem cell differentiation and development, and provides an outlook on how this process could be mechanistically regulated.