Extracellular nucleotides affect myogenesis.

Extracellular nucleotides exert important biological actions in several cell systems. Signalling of extracellular nucleotides occurs through the activation of specific cell surface receptors. Two families of nucleotide receptors, P2X and P2Y, have been described which are associated to diverse signal transduction pathways. When activated, ionotropic P2X receptors (P2X1-7) form non selective channels permeable to Ca2+ and Na+, while metabotropic P2Y receptors are functionally coupled either to phospholipase C (P2Y1, 2, 4, 6, and 11) or to adenylate cyclase (P2Y12-14). The overall signalling action of nucleotides is under the control of ectonucleotidases (NTPDases), a family of enzymes that by degrading nucleotides terminate the signalling. Growing evidence shows the occurrence of extracellular nucleotides signalling in skeletal muscle. In the present work, this signalling was characterized in differentiating C2C12 cells. Mechanical or electrical stimulation of C2C12 myotubes produced significant release of ATP, while it was without effects in myoblasts. The ecto-ATPase activity of cells progressively increased in parallel with differentiation. Consistently, the expression level of NTPDases (1, 2 and 3 and of a-sarcoglycan) also increased. Responsiveness to nucleotides changed dramatically during differentiation, consistent with substantial changes in the expression of P2X and P2Y receptors. Nucleotide appears to stimulate proliferation of myoblasts, while the prolonged exposure to and excessive levels of ATP seems to compromise the survival of myotubes. Funded by TELETHON ITALY.