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J Physiol Volume 572, Number 3, 721-733, May 1, 2006 DOI: 10.1113/jphysiol.2005.102194
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Neuroscience

Extracellular guanosine-5'-triphosphate modulates myogenesis via intermediate Ca2+-activated K+ currents in C2C12 mouse cells

Tiziana Pietrangelo1, Bernard Fioretti2, Rosa Mancinelli1, Luigi Catacuzzeno2, Fabio Franciolini2, Giorgio Fanò3 and Stefania Fulle1

1 Dipartimento Scienze del Farmaco
3 Centro Universitario Medicina dello Sport, Istituto Interuniversitario di Miologia, Ce.S.I. Centro di Scienze dell'Invecchiamento ‘University G. d'Annunzio’ Foundation, via dei Vestini, I-66013 Chieti, Italy
2 Dipartimento di Biologia Cellulare e Ambientale, Università di Perugia, via Pascoli 1, I-06123 Perugia, Italy

In this study we investigated the role of extracellular 5'-guanosine-triphosphate (GTP) on early phases of skeletal muscle differentiation using the widely used C2C12 mouse cells as a myogenic model. We show that extracellular GTP binding to specific sites activates a metabotropic cascade that leads to a transient intracellular Ca2+ mobilization, consequent activation of the intermediate Ca2+-activated K+ channels (IKCa), and hyperpolarization of the plasma membrane. We further show that in differentiating C2C12 myoblasts GTP induces a proliferative boost, and increases the number of cells positive for the myosin heavy chain (MyHC) proteins. These effects were shown to be mediated by the IKCa channel-dependent hyperpolarization, as evidenced by their disappearance when myoblasts were incubated with the IKCa channel inhibitor charybdotoxin. These data give new insights into nucleotide purinergic signalling pathways, and address the role of the GTP-dependent IKCa channel activation and hyperpolarization in myogenesis.

(Received 22 November 2005; accepted after revision 31 January 2006; first published online 2 February 2006)
Corresponding author T. Pietrangelo: Ce.S.I. (Centro di Scienze dell'Invecchiamento), ‘Università G. d'Annunzio’ Foundation, Via Colle dell'Ara, I-66013 Chieti, Italy. Email: tiziana{at}unich.it






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