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Published 22 July 2002. doi:10.1083/jcb.200202025
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© The Rockefeller University Press, 0021-9525/2002/7/345 $5.00
The Journal of Cell Biology, Volume 158, Number 2, July 22, 2002 345-355

Article

ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells



Mina Ryten1, Philip M. Dunn1, Joseph T. Neary2 and Geoffrey Burnstock1

1 Autonomic Neuroscience Institute, Royal Free and University College Medical School, London NW3 2PF, U.K.
2 Research Service, VA Medical Center and Departments of Pathology, Biochemistry, and Molecular Biology and Neuroscience Program, University of Miami School of Medicine, Miami, FL

Address correspondence to Geoffrey Burnstock, Autonomic Neuroscience Institute, Royal Free and University College Medical School, Royal Free Campus, Rowland Hill Street, London NW3 2PF, U.K. Tel.: 44-20-7830-2948. Fax: 44-20-7830-2949. E-mail: g.burnstock{at}ucl.ac.uk

ATP is well known for its role as an intracellular energy source. However, there is increasing awareness of its role as an extracellular messenger molecule (Burnstock, 1997). Although evidence for the presence of receptors for extracellular ATP on skeletal myoblasts was first published in 1983 (Kolb and Wakelam), their physiological function has remained unclear. In this paper we used primary cultures of rat skeletal muscle satellite cells to investigate the role of purinergic signaling in muscle formation. Using immunocytochemistry, RT-PCR, and electrophysiology, we demonstrate that the ionotropic P2X5 receptor is present on satellite cells and that activation of a P2X receptor inhibits proliferation, stimulates expression of markers of muscle cell differentiation, including myogenin, p21, and myosin heavy chain, and increases the rate of myotube formation. Furthermore, we demonstrate that ATP application results in a significant and rapid increase in the phosphorylation of MAPKs, particularly p38, and that inhibition of p38 activity can prevent the effect of ATP on cell number. These results not only demonstrate the existence of a novel regulator of skeletal muscle differentiation, namely ATP, but also a new role for ionotropic P2X receptors in the control of cell fate.

Key Words: ATP; P2X5; skeletal muscle; differentiation; satellite cells


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