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

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-a-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-a-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.