Barbara Norman

Strength, power, fiber types, and mRNA expression in trained men and women with different ACTN3 R577X genotypes

Alpha-actinins are structural proteins of the Z-line. Human skeletal muscle expresses two alpha-actinin isoforms, alpha-actinin-2 and alpha-actinin-3, encoded by their respective genes ACTN2 and ACTN3. ACTN2 is expressed in all muscle fiber types, while only type II fibers, and particularly the type IIb fibers, express ACTN3. ACTN3 (R577X) polymorphism results in loss of alpha-actinin-3 and has been suggested to influence skeletal muscle function. The X allele is less common in elite sprint and power athletes than in the general population and has been suggested to be detrimental for performance requiring high power. The present study investigated the association of ACTN3 genotype with muscle power during 30-s Wingate cycling in 120 moderately to well-trained men and women and with knee extensor strength and fatigability in a subset of 21 men performing isokinetic exercise. Muscle biopsies were obtained from the vastus lateralis muscle to determine fiber-type composition and ACTN2 and ACTN3 mRNA levels. Peak and mean power and the torque-velocity relationship and fatigability output showed no difference across ACTN3 genotypes. Thus this study suggests that R577X polymorphism in ACTN3 is not associated with differences in power output, fatigability, or force-velocity characteristics in moderately trained individuals. However, repeated exercise bouts prompted an increase in peak torque in RR but not in XX genotypes, suggesting that ACTN3 genotype may modulate responsiveness to training. Our data further suggest that alpha-actinins do not play a significant role in determining muscle fiber-type composition. Finally, we show that ACTN2 expression is affected by the content of alpha-actinin-3, which implies that alpha-actinin-2 may compensate for the lack of alpha-actinin-3 and hence counteract the phenotypic consequences of the deficiency.

ACTN3 genotype and modulation of skeletal muscle response to exercise in human subjects.

α-Actinin-3 is a Z-disc protein expressed only in type II muscle fibers. A polymorphism in the ACTN3 gene (R577X) results in lack of α-actinin-3 in XX genotype. The prevalence of the mutated X-allele is lower among power/sprint oriented athletes compared with controls, indicating that the lack of α-actinin-3 is detrimental in these sports, but a mechanistic link has not been established. Results from Actn3-knockout (KO) mouse model suggest that α-actinin-3 may affect muscle mass and muscle glycogen levels. In the present investigation we examined muscle fiber type composition, cross-sectional fiber area (CSA), and muscle glycogen levels at baseline in 143 human subjects with different ACTN3 genotypes. In addition, hypertrophy signaling and glycogen utilization in response to sprint exercise were studied in a subset of subjects. Glycogen utilization was analyzed in separate pools of type I and type II fibers. No differences in fiber type composition, CSA, or muscle glycogen levels were observed at baseline across the ACTN3 genotypes. However, the sprint exercise-induced increase in phosphorylation of mTOR and p70S6k was smaller in XX than in RR+RX (P = 0.03 and P = 0.01, respectively), indicating a less pronounced activation of hypertrophy signaling in XX. Glycogen utilization during sprint exercise varied across ACTN3 genotypes in type II fibers (P = 0.03) but not in type I fibers (P = 0.38). The present results are in accordance with findings from the KO mice and reinforce the hypothesis that ACTN3 genotype-associated differences in muscle mass and glycogen utilization provide a mechanistic explanation for the modulation of human performance by the ACTN3 genotype.

Greater growth hormone and insulin response in women than in men during repeated bouts of sprint exercise

Aim:  In a previous study, sprint training has been shown to increase muscle cross‐sectional area in women but not in men [Eur J Appl Physiol Occup Physiol 74 (1996) 375]. We hypothesized that sprint exercise induces a different hormonal response in women than in men. Such a difference may contribute to explaining the observed gender difference in training response.

Contraction-mediated glycogenolysis in mouse skeletal muscle lacking creatine kinase: the role of phosphorylase b activation

Skeletal muscle that is deficient in creatine kinase (CK−/−) exhibits accelerated glycogenolysis during contraction. Understanding this phenomenon could provide insight into the control of glycogenolysis during contraction. Therefore, glycogen breakdown was investigated in isolated extensor digitorum longus CK−/− muscle. Muscles were stimulated to produce repeated tetani for 20 s in the presence of sodium cyanide to block mitochondrial respiration. Accumulation of lactate after stimulation was similar in wild‐type (WT) and CK−/− muscles, whereas accumulation of glucose‐6‐phosphate was twofold higher in CK−/− muscles, indicating greater glycogenolysis in CK−/− muscles. Total phosphorylase activity was decreased by almost 30 % in CK−/− muscle (P < 0.001). Phosphorylase fractional activity (−/+ 3.3 mm AMP) was similar in both groups in the basal state (about 10 %), but increased to a smaller extent in CK−/− muscles after stimulation (39 ± 4 % vs. 52 ± 4 % in WT, P < 0.05). Inorganic phosphate, the substrate for phosphorylase, increased marginally in CK−/− muscles after stimulation (basal = 25.3 ± 2.2 µmol (g dry muscle)−1; stimulated = 33.9 ± 2.3 µmol (g dry muscle)−1), but substantially in WT muscles (basal = 11.4 ± 0.7 µmol (g dry muscle)−1; stimulated = 54.2 ± 4.5 µmol (g dry muscle)−1). Kinetic studies of phosphorylase b (dephosphorylated enzyme) from muscle extracts in vitro demonstrated higher relative activities in CK−/− muscles (60–135 %) in response to low AMP concentrations (up to 50 µm) in both the basal state and after stimulation (P < 0.05), whereas no differences in activity between CK−/− and WT muscles were observed at high AMP concentrations (> 100 µm). These data indicate that allosteric activation of phosphorylase b accounts for the accelerated glycogenolysis in CK−/− muscle during contraction.

Beta-alanine supplementation improves jumping power and affects severe-intensity performance in professional alpine skiers.

INTRODUCTION Supplementation with beta-alanine may have positive effects on severe-intensity, intermittent, and isometric strength-endurance performance. These could be advantageous for competitive alpine skiers, whose races last 45 to 150 s, require metabolic power above the aerobic maximum, and involve isometric muscle work. Further, beta-alanine supplementation affects the muscle force-frequency relationship, which could influence explosiveness. We explored the effects of beta-alanine on explosive jump performance, severe exercise energy metabolism, and severe-intensity ski-like performance. METHODS Nine male elite alpine skiers consumed 4.8 g/d beta-alanine or placebo for 5 weeks in a double-blind fashion. Before and after, they performed countermovement jumps (CMJ), a 90-s cycling bout at 110% VO2max (CLT), and a maximal 90-s box jump test (BJ90). RESULTS Beta-alanine improved maximal (+7 ± 3%, d = 0.9) and mean CMJ power (+7 ± 2%, d = 0.7), tended to reduce oxygen deficit (-3 ± 8%, p = .06) and lactate accumulation (-12 ± 31%) and enhance aerobic energy contribution (+1.3 ± 2.9%, p = .07) in the CLT, and improved performance in the last third of BJ90 (+7 ± 4%, p = .02). These effects were not observed with placebo. CONCLUSIONS Beta-alanine supplementation improved explosive and repeated jump performance in elite alpine skiers. Enhanced muscle contractility could possibly explain improved explosive and repeated jump performance. Increased aerobic energy production could possibly help explain repeated jump performance as well.

Elevations of local intravascular pressures release vasoactive substances in humans

The wall stiffness of arteries and arterioles adapts to the long‐term demands imposed by local intravascular pressure. We investigated whether substances capable of inducing acute and long‐term effects on arterial wall stiffness are released locally into the bloodstream in response to an acute marked increase in local intravascular pressure in the blood vessels of the human arm. Experiments were performed on ten subjects positioned in a pressure chamber with one arm extended through a hole in the chamber door and kept at normal atmospheric pressure. Intravascular pressure was increased in the arm, by a stepwise increase in chamber pressure up to +150 mmHg. Diameter and flow were measured in the brachial artery by Doppler ultrasonography. Blood samples were drawn simultaneously from both arms before, during, immediately after and 2 h after the release of the chamber pressure. Plasma levels of endothelin‐1 (ET‐1), vascular endothelial growth factor A (VEGF‐A), fibroblast growth factor 2 (FGF‐2) and angiotensin II (Ang‐II) were measured. Elevation of chamber pressure by 150 mmHg increased local arterial distending pressure to about 220–260 mmHg, resulting in an increase in brachial artery diameter of 9% and flow of 246%. The pressure stimulus increased the plasma levels of ET‐1 and Ang‐II, but not of VEGF‐A or FGF‐2 in the test arm. The local release of the vasoconstrictors ET‐1 and Ang‐II in response to markedly increased distending pressure may reflect one mechanism behind adaptation to acute and long‐term changes in intravascular pressure.

Long-term intermittent hyperoxic exposures do not enhance erythropoiesis

Eur J Clin Invest 2012; 42 (3): 260–265