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doi: 10.1242/10.1242/dev.00562

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Acceleration of human myoblast fusion by depolarization: graded Ca²⁺ signals involved

Jian-Hui Liu^1,2, Stéphane König^1,*, Marlène Michel^1,*, Serge Arnaudeau¹, Jacqueline Fischer-Lougheed¹, Charles R. Bader² and Laurent Bernheim^1,

¹ Département de Physiologie, Centre Médical Universitaire, Hôpital Cantonal Universitaire, CH-1211 Geneva 4, Switzerland
² Division de Recherche Clinique Neuro-Musculaire, Département des Neurosciences, Cliniques et Dermatologie, Hôpital Cantonal Universitaire, CH-1211 Geneva 4, Switzerland

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

Accepted 24 April 2003

We have previously shown that human myoblasts do not fuse when their voltage fails to reach the domain of a window T-type Ca²⁺ current. We demonstrate, by changing the voltage in the window domain, that the Ca²⁺ signal initiating fusion is not of the all-or-none type, but can be graded and is interpreted as such by the differentiation program. This was carried out by exploiting the properties of human ether-à-go-go related gene K⁺ channels that we found to be expressed in human myoblasts. Methanesulfonanilide class III antiarrhythmic agents or antisense-RNA vectors were used to suppress completely ether-à-go-go related gene current. Both procedures induced a reproducible depolarization from -74 to -64 mV, precisely in the window domain where the T-type Ca²⁺ current increases with voltage. This 10 mV depolarization raised the cytoplasmic free Ca²⁺ concentration, and triggered a tenfold acceleration of myoblast fusion. Our results suggest that any mechanism able to modulate intracellular Ca²⁺ concentration could affect the rate of myoblast fusion.

Key words: Ca²⁺ current, Herg, Muscle differentiation, Myoblast fusion, Window current

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