Fulton 2019 Abstract IOC139
|Fulton MR, Davis MS (2019) Effect of hyperthermia on mitochondrial function in canine skeletal muscle. Mitochondr Physiol Network 24.01.|
Skeletal muscle can experience a 20-fold range of rate of metabolic heat production in athletes, subjecting mitochondria to levels of hyperthermia that likely alter oxidative phosphorylation (OxPhos). The exact nature of these alterations are likely temperature-dependent, as potential increases in enzyme activity are eventually offset by thermal damage. Specifically, we hypothesize that one result of increased temperature is an increase in proton leak across the mitochondrial membrane. However, well-conditioned athletes are known to be more tolerant to hyperthermia, but it is unknown whether this ability to preserve athletic function during heat stress is due to greater mitochondrial tolerance to hyperthermia. A previous study with racing sled dogs showed that at a single temperature of 37°C, proton leak decreased as fitness levels increased. Thus, this study is part of a project to test the hypothesis that athletic conditioning results in greater mitochondrial OxPhos capacity at high temperatures.
Eight fully conditioned Alaskan sled dogs were used to evaluate the effect of ex vivo hyperthermia on skeletal muscle OxPhos. Skeletal muscle biopsies were obtained from the biceps femoris muscle after 7 months of progressive endurance conditioning that included competition in the annual 1000-mile Iditarod sled dog race. The biopsies were permeabilized and analyzed using high resolution respirometry at 4 different incubation temperatures (38, 40, 42, and 44°C) using standard SUIT protocols. Effect of incubation temperature was analyzed using repeated measures one-way ANOVA and post-hoc pairwise comparisons using Tukey’s correction for multiple comparisons.
Six of the eight dogs used in this study completed the 1000-mile race in 11 days, 10 hr (22nd place), with the other 2 dogs having completed approximately 300 miles before being removed from the team due to injury. Respirometry measurements for one dog was limited to PGML and PGMP due to technical problems during analysis. At 38°C (the normal body temperature of a dog), the respiratory states PGML, PGMP, PGMSP, and SP resulted in 29.4 ± 5.2, 106.8 ± 47.1 184.4 ± 52.3, and 100.6 ± 32.0 pmol/mg/sec of oxygen flux, respectively. PGML was strongly affected by temperature (p<0.0001), with a maximum value of 49.5 ± 8.8 at 44°C. No other respiratory states were significantly affected by incubation temperature.
Data collected from this study show that hyperthermia induces spontaneous OXPHOS uncoupling in canine skeletal muscle. We cannot definitively say where proton leak is occurring at this moment and the implications of increasing proton leak during hyperthermia are not understood fully at this time, but it is known in other species that increased membrane potential is associated with hydrogen peroxide production and therefore leads to oxidative damage to the mitochondria. Concurrent mitochondrial membrane potential measurements could aid in discovering the consequences of proton leak on mitochondrial function. Studies are scheduled to repeat these measurements in the same dogs in a deconditioned state to further characterize the effects of athletic conditioning on temperature-dependent mitochondrial OxPhos.
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style
Organism: Dog Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
- Depart Physiological Sciences, Oklahoma State Univ, Stillwater, OK, USA