Mesenchymal stem cell differentiation: Control by calcium-activated potassium channels

Mesenchymal stem cells (MSCs) are widely used in modern medicine for which understanding the mechanisms controlling their differentiation is fundamental. Ion channels offer novel insights to this process because of their role in modulating membrane potential and intracellular milieu. Here, we evaluate the contribution of calcium-activated potassium (K-Ca) channels to the three main components of MSC differentiation: initiation, proliferation, and migration. First, we demonstrate the importance of the membrane potential (V-m) and the apparent association of hyperpolarization with differentiation. Of K-Ca subtypes, most evidence points to activity of big-conductance channels in inducing initiation. On the other hand, intermediate-conductance currents have been shown to promote progression through the cell cycle. While there is no information on the role of K-Ca channels in migration of MSCs, work from other stem cells and cancer cells suggest that intermediate-conductance and to a lesser extent big-conductance channels drive migration. In all cases, these effects depend on species, tissue origin and lineage. Finally, we present a conceptual model that demonstrates how K-Ca activity could influence differentiation by regulating V-m and intracellular Ca2+ oscillations. We conclude that K-Ca channels have significant involvement in MSC differentiation and could potentially enable novel tissue engineering approaches and therapies.