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.
Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals involved Available to Purchase
These authors contributed equally to the work
Jian-Hui Liu, Stéphane König, Marlène Michel, Serge Arnaudeau, Jacqueline Fischer-Lougheed, Charles R. Bader, Laurent Bernheim; Acceleration of human myoblast fusion by depolarization: graded Ca2+ signals involved. Development 1 August 2003; 130 (15): 3437–3446. doi: https://doi.org/10.1242/dev.00562
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