title: A gene for speed: contractile properties of isolated whole EDL muscle from an alpha-actinin-3 knockout mouse.
abstract: The actin-binding protein alpha-actinin-3 is one of the two isoforms of alpha-actinin that are found in the Z-discs of skeletal muscle. alpha-Actinin-3 is exclusively expressed in fast glycolytic muscle fibers. Homozygosity for a common polymorphism in the ACTN3 gene results in complete deficiency of alpha-actinin-3 in about 1 billion individuals worldwide. Recent genetic studies suggest that the absence of alpha-actinin-3 is detrimental to sprint and power performance in elite athletes and in the general population. In contrast, alpha-actinin-3 deficiency appears to be beneficial for endurance athletes. To determine the effect of alpha-actinin-3 deficiency on the contractile properties of skeletal muscle, we studied isolated extensor digitorum longus (fast-twitch) muscles from a specially developed alpha-actinin-3 knockout (KO) mouse. alpha-Actinin-3-deficient muscles showed similar levels of damage to wild-type (WT) muscles following lengthening contractions of 20% strain, suggesting that the presence or absence of alpha-actinin-3 does not significantly influence the mechanical stability of the sarcomere in the mouse. alpha-Actinin-3 deficiency does not result in any change in myosin heavy chain expression. However, compared with alpha-actinin-3-positive muscles, alpha-actinin-3-deficient muscles displayed longer twitch half-relaxation times, better recovery from fatigue, smaller cross-sectional areas, and lower twitch-to-tetanus ratios. We conclude that alpha-actinin-3 deficiency results in fast-twitch, glycolytic fibers developing slower-twitch, more oxidative properties. These changes in the contractile properties of fast-twitch skeletal muscle from alpha-actinin-3-deficient individuals would be detrimental to optimal sprint and power performance, but beneficial for endurance performance.
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Chan
authors.forename: J T
authors.initials: JT
authors.lastname: Seto
authors.forename: D G
authors.initials: DG
authors.lastname: MacArthur
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.forename: K N
authors.initials: KN
authors.lastname: North
authors.forename: S I
authors.initials: SI
authors.lastname: Head
mesh_terms: D000185:Actinin / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics* / Q000502:physiology; D018763:Muscle Fatigue / Q000235:genetics / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*
chemical_list: C525925:Actn3 protein, mouse; D000185:Actinin