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 Ca(2+) current. We demonstrate, by changing the voltage in the window domain, that the Ca(2+) 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 Ca(2+) current increases with voltage. This 10 mV depolarization raised the cytoplasmic free Ca(2+) concentration, and triggered a tenfold acceleration of myoblast fusion. Our results suggest that any mechanism able to modulate intracellular Ca(2+) concentration could affect the rate of myoblast fusion.
Liu
Jian-Hui
JH
Département de Physiologie, Centre Médical Universitaire, Hôpital Cantonal Universitaire, CH-1211 Geneva 4, Switzerland.
König
Stéphane
S
Michel
Marlène
M
Arnaudeau
Serge
S
Fischer-Lougheed
Jacqueline
J
Bader
Charles R
CR
Bernheim
Laurent
L
D002118:Calcium / Q000378:metabolism*; D027682:Cation Transport Proteins; D002459:Cell Fusion; D003593:Cytoplasm / Q000502:physiology; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D024510:Muscle Development / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D002118:Calcium