Inositol 1,4,5 trisphosphate receptor 1 is a key player of human myoblast differentiation

Cytosolic Ca2+ signals are fundamental for the early and late steps of myoblast differentiation and are, as in many cells, generated by Ca2+ release from internal stores as well as by plasma membrane Ca2+ entry. Our recent studies identified the store-operated Ca2+ channels, Orai1 and TRPC1&C4, as crucial for the early steps of human myogenesis and for the late fusion events. In the present work, we assessed the role of the inositol-1,4,5 tris-phosphate receptor (IP3R) type 1 during human myoblast differentiation. We demonstrated, using siRNA strategy that IP(3)R1 is required for the expression of muscle-specific transcription factors such as myogenin and MEF2 (myocyte enhancer factor 2), and for the formation of myotubes. The knockdown of IP(3)R1 strongly reduced endogenous spontaneous Ca2+ transients, and attenuated store-operated Ca2+ entry. As well, two Ca2+-dependent key enzymes of muscle differentiation, NFAT and CamKII are down-regulated upon siIP(3)R1 treatment. On the contrary, the overexpression of IP(3)R1 accelerated myoblasts differentiation. These findings identify Ca2+ release mediated by IP(3)R1 as an essential mechanism during the early steps of myoblast differentiation. (C) 2014 Elsevier Ltd. All rights reserved.