title: Defective excitation-contraction coupling is partially responsible for impaired contractility in hindlimb muscles of Stac3 knockout mice.
abstract: The Stac3 gene is exclusively expressed in skeletal muscle, and Stac3 knockout is perinatal lethal in mice. Previous data from Stac3-deleted diaphragms indicated that Stac3-deleted skeletal muscle could not contract because of defective excitation-contraction (EC) coupling. In this study, we determined the contractility of Stac3-deleted hindlimb muscle. In response to frequent electrostimulation, Stac3-deleted hindlimb muscle contracted but the maximal tension generated was only 20% of that in control (wild type or heterozygous) muscle (P < 0.05). In response to high [K(+)], caffeine, and 4-chloro-m-cresol (4-CMC), the maximal tensions generated in Stac3-deleted muscle were 29% (P < 0.05), 58% (P = 0.08), and 55% (P < 0.05) of those in control muscle, respectively. In response to 4-CMC or caffeine, over 90% of myotubes formed from control myoblasts contracted, but only 60% of myotubes formed from Stac3-deleted myoblasts contracted (P = 0.05). However, in response to 4-CMC or caffeine, similar increases in intracellular calcium concentration were observed in Stac3-deleted and control myotubes. Gene expression and histological analyses revealed that Stac3-deleted hindlimb muscle contained more slow type-like fibers than control muscle. These data together confirm a critical role of STAC3 in EC coupling but also suggest that STAC3 may have additional functions in skeletal muscle, at least in the hindlimb muscle.
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Doering
authors.affiliation: Department of Human Nutrition, Foods, and Exercise, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Grange
authors.affiliation: Department of Animal and Poultry Sciences, Virginia Tech, Blacksburg, VA, USA.
authors.forename: Honglin
authors.initials: H
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D056966:Excitation Contraction Coupling; D006614:Hindlimb / Q000473:pathology* / Q000503:physiopathology*; D006651:Histocytochemistry; D018345:Mice, Knockout; D009132:Muscles / Q000473:pathology* / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000172:deficiency*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; C583601:STAC3 protein, mouse