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Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres.

ABSTRACT: A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Err?) on the myostatin (Mtn) mouse null background (Mtn(-/-)/Err?(Tg/+)) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn(-/-)/Err?(Tg/+) mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.

SUBMITTER: Omairi S

PROVIDER: S-EPMC4975572 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres.

Omairi Saleh S Matsakas Antonios A Degens Hans H Kretz Oliver O Hansson Kenth-Arne KA Solbrå Andreas Våvang AV Bruusgaard Jo C JC Joch Barbara B Sartori Roberta R Giallourou Natasa N Mitchell Robert R Collins-Hooper Henry H Foster Keith K Pasternack Arja A Ritvos Olli O Sandri Marco M Narkar Vihang V Swann Jonathan R JR Huber Tobias B TB Patel Ketan K

eLife 20160805

A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn(-/-)/Errγ(Tg/+)) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canon ...[more]

PMID: 27494364

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Project description:Acid-sensing ion channel (ASIC) proteins form extracellular proton-gated, cation-selective channels in neurons and vascular smooth muscle cells and are proposed to act as extracellular proton sensors. However, their importance to vascular responses under conditions associated with extracellular acidosis, such as strenuous exercise, is unclear. Therefore, the purpose of this study was to determine if one ASIC protein, ASIC1a, contributes to extracellular proton-gated vascular responses and exercise tolerance. To determine if ASIC1a contributes to exercise tolerance, we determined peak oxygen (O2) uptake in conscious ASIC1a-/- mice during exhaustive treadmill running. Loss of ASIC1a was associated with a greater peak running speed (60 ± 2 vs. 53 ± 3 m·min-1, P = 0.049) and peak oxygen (O2) uptake during exhaustive treadmill running (9563 ± 120 vs. 8836 ± 276 mL·kg-1·h-1, n = 6-7, P = 0.0082). There were no differences in absolute or relative lean body mass, as determined by EchoMRI. To determine if ASIC1a contributes to vascular responses during muscle contraction, we measured femoral vascular conductance (FVC) during a stepwise electrical stimulation (0.5-5.0 Hz at 3 V for 60 sec) of the left major hind limb muscles. FVC increased to a greater extent in ASIC1a-/- versus ASIC1a+/+ mice (0.44 ± 0.03 vs. 0.30 ± 0.04 mL·min-1·100 g hind limb mass-1 · mmHg-1, n = 5 each, P = 0.0009). Vasodilation following local application of external protons in the spinotrapezius muscle increased the duration, but not the magnitude, of the vasodilatory response in ASIC1a-/- mice. Finally, we examined hind limb vascular density using micro-CT and found increased density of 0-80 μm vessels (P < 0.05). Our findings suggest an increased vascular density and an enhanced vasodilatory response to local protons, to a lesser degree, may contribute to the enhanced vascular conductance and increased peak exercise capacity in ASIC1a-/- mice.

Dataset Information

Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres.

Publications

Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres.

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