Bone marrow-derived mesenchymal stem cells (MSC) can be differentiated into myocytes, as well as adipocytes, chondrocytes, and osteocytes in culture. Calcium channels mediate excitation-contraction coupling and are essential for the function of muscle. However, little is known about the expression of calcium channel subunits and calcium handling in stem cells. We examined whether the expression of calcium channel subunits in MSC is similar to that of skeletal muscle satellite cells and if their levels of expression are modified after treatment with bone morphogenetic protein-4 (BMP4). We found that during myogenic differentiation, MSC first express the α2δ1 subunit and the cardiac channel subunit Cav1.2. In contrast to the α2δ1 subunit levels, the Cav1.2 subunit decreases rapidly with time. The skeletal channel subunit Cav1.1 is detected at day 3 but its expression increases considerably, resembling more closely the expression of the subunits in satellite cells. Treatment of MSC with BMP4 caused a significant increase in expression of Cav1.2, a delay in expression of Cav1.1, and a reduction in the duration of calcium transients when extracellular calcium was removed. Calcium currents and transients followed a pattern related to the expression of the cardiac (Cav1.2) or skeletal (Cav1.1) α1subunits. These results indicate that differentiation of untreated MSC resembles differentiation of skeletal muscle and that BMP4 reduces skeletal muscle calcium channel expression and promotes the expression of cardiac calcium channels during myogenic differentiation.
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The authors want to thank Santipongse Chatchavalvanich for his help with the initial experiments. This work was funded by NIH training grant (2 T32 HL7692-21; PI: Solaro, R. J.) and by the Illinois Department of Public Health (P.I. D.L. Geenen), NHLBI (R01 HL071046; P.I. D.L. Geenen), and Muscular Dystrophy Association, Inc. (P.I. J. García).
The authors indicate no potential conflicts of interest.
David L. Geenen and Jesús García Co-senior authors
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Grajales, L., Lach, L.E., Janisch, P. et al. Temporal Expression of Calcium Channel Subunits in Satellite Cells and Bone Marrow Mesenchymal Cells. Stem Cell Rev and Rep 11, 408–422 (2015). https://doi.org/10.1007/s12015-014-9566-4
- Calcium channels
- Mesenchymal stem cells
- Satellite cells
- Cardiac myogenesis
- Skeletal myogenesis
- Calcium release
- Bone morphogenetic protein-4