The general goal of our lab is to study skeletal muscle regeneration. Our specific current objective is to understand the role of ionic channels in the early stages of human myoblast differentiation and fusion. Our starting material is the satellite cell, the myogenic stem cell of skeletal muscle. Upon muscle injury, satellite cells proliferate as myoblasts and, after a process of differentiation, fuse together to generate new muscle fibers. We discovered that a membrane hyperpolarization is among the earliest steps in myoblast differentiation, and that this hyperpolarization is required for the differentiation process to take place. Membrane hyperpolarization results from an up-regulation of Kir2.1 inward rectifying potassium channels and is used by the cell to promote calcium influxes. These calcium influxes, in turn, via the calcineurin pathway, activate the myogenic transcription factors myogenin and MEF2, two transcription factors crucial for myoblast differentiation.
