Ontogenesis and localization of Ca2+ channels in mammalian skeletal muscle in culture and role in excitation-contraction coupling.
The mechanism of excitation-contraction (E-C) coupling in skeletal muscle is not yet well established. Cultured mouse skeletal muscle cells have been used to study the relationships between triad formation, Ca2+ channel activities, and contractions. The ontogenesis of voltage-dependent Ca2+ channels and their localization in relation to the ability of muscle to contract and the ultrastructural organization of sarcomeres and triads have been investigated by using an electrophysiological approach together with an electron microscope study. At an early stage of development, both fast (Ifast) and slow (Islow) types of Ca2+ channels are found at the surface membrane. At later stages of development, fast Ca2+ channels remain at the surface membrane, while slow Ca2+ channels migrate to the transverse-tubule membrane. The voltage dependence of fast Ca2+ channels compared to the voltage dependence of contraction clearly shows that these Ca2+ channels have no direct role in E-C coupling. Detubulation at all stages of development has confirmed that T tubules contain essential elements for E-C coupling. However, this work also shows that Ca2+ flowing through slow Ca2+ channels situated in the T-tubular system is not important for contraction. Myotubes lacking slow Ca2+ channels or having no slow Ca2+ channel transport activity (jumps to high membrane potentials, no external Ca2+, block of Islow by Co2+) still retain contraction.
Romey
G
G
Centre de Biochimie, Centre National de la Recherche Scientifique, Nice, France.
Garcia
L
L
Dimitriadou
V
V
Pincon-Raymond
M
M
Rieger
F
F
Lazdunski
M
M
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004553:Electric Conductivity; D008564:Membrane Potentials; D051379:Mice; D008854:Microscopy, Electron; D009119:Muscle Contraction; D009132:Muscles / Q000166:cytology / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000648:ultrastructure
D015220:Calcium Channels; D011978:Receptors, Nicotinic; D002118:Calcium