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First published online 23 January 2008
doi: 10.1242/dev.011387

Development 135, 859-867 (2008)
Published by The Company of Biologists 2008
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Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242

Valérie Hinard1, Dominique Belin2, Stéphane Konig1, Charles Roland Bader3 and Laurent Bernheim1,*

1 Département de Neurosciences Fondamentales, University of Geneva, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland.
2 Département de Pathologie et Immunologie, University of Geneva, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland.
3 Département des Neurosciences Cliniques, University of Geneva, Centre Médical Universitaire, CH-1211 Geneva 4, Switzerland.

* Author for correspondence (e-mail: laurent.bernheim{at}medecine.unige.ch)

Accepted 18 December 2007

Myoblast differentiation is essential to skeletal muscle formation and repair. The earliest detectable event leading to human myoblast differentiation is an upregulation of Kir2.1 channel activity, which causes a negative shift (hyperpolarization) of the resting potential of myoblasts. After exploring various mechanisms, we found that this upregulation of Kir2.1 was due to dephosphorylation of the channel itself. Application of genistein, a tyrosine kinase inhibitor, increased Kir2.1 activity and triggered the differentiation process, whereas application of bpV(Phen), a tyrosine phosphatase inhibitor, had the opposite effects. We could show that increased Kir2.1 activity requires dephosphorylation of tyrosine 242; replacing this tyrosine in Kir2.1 by a phenylalanine abolished inhibition by bpV(Phen). Finally, we found that the level of tyrosine phosphorylation in endogenous Kir2.1 channels is considerably reduced during differentiation when compared with proliferation. We propose that Kir2.1 channels are already present at the membrane of proliferating, undifferentiated human myoblasts but in a silent state, and that Kir2.1 tyrosine 242 dephosphorylation triggers differentiation.

Key words: Human myoblasts, Hyperpolarization, Myoblast differentiation, Potassium channel, Tyrosine phosphorylation




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V. Hinard, D. Belin, S. Konig, C. R. Bader, and L. Bernheim
Initiation of human myoblast differentiation via dephosphorylation of Kir2.1 K+ channels at tyrosine 242
J. Cell Sci., March 1, 2008; 121(5): e1 - e1.
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