Department of Biology, McMaster University, Hamilton, ON, Canada.
Acta Physiol (Oxf). 2018 May;223(1):e13030. doi: 10.1111/apha.13030. Epub 2018 Feb 1.
We examined the effects of chronic hypoxia on diaphragm function in high- and low-altitude populations of Peromyscus mice.
Deer mice (P. maniculatus) native to high altitude and congeneric mice native to low altitude (P. leucopus) were born and raised in captivity to adulthood and were acclimated to normoxia or hypobaric hypoxia (12 or 9 kPa, simulating hypoxia at 4300 and 7000 m) for 6-8 weeks. We then measured indices of mitochondrial respiration capacity, force production, and fatigue resistance in the diaphragm.
Mitochondrial respiratory capacities (assessed using permeabilized fibres with single or multiple inputs to the electron transport system), citrate synthase activity (a marker of mitochondrial volume), twitch force production, and muscle fatigue resistance increased after exposure to chronic hypoxia in both populations. These changes were not well explained by variation in the fibre-type composition of the muscle. However, there were several differences in diaphragm function in high-altitude mice compared to low-altitude mice. Exposure to a deeper level of hypoxia (9 kPa vs 12 kPa) was needed to elicit increases in mitochondrial respiration rates in highlanders. Chronic hypoxia did not increase the emission of reactive oxygen species from permeabilized fibres in highlanders, in contrast to the pronounced increases that occurred in lowlanders. In general, the diaphragm of high-altitude mice had greater capillary length densities, produced less force in response to stimulation and had shorter relaxation times. The latter was associated with higher activity of sarcoplasmic reticulum Ca -ATPase (SERCA) activity in the diaphragm of high-altitude mice.
Overall, our work suggests that exposure to chronic hypoxia increases the capacities for mitochondrial respiration, force production and fatigue resistance of the diaphragm. However, many of these effects are opposed by evolved changes in diaphragm function in high-altitude natives, such that highlanders in chronic hypoxia maintain similar diaphragm function to lowlanders in sea level conditions.
我们研究了慢性低氧对高海拔和低海拔鼠属 Peromyscus 小鼠膈肌功能的影响。
从高海拔地区捕获并饲养鹿鼠（P. maniculatus）和低海拔地区捕获并饲养近亲鼠（P. leucopus），使其在低氧舱中适应常氧或低氧（12 或 9 kPa，模拟海拔 4300 和 7000 米的低氧）6-8 周。然后测量膈肌的线粒体呼吸能力、产力和抗疲劳能力的指标。
在两种种群中，暴露于慢性低氧后，线粒体呼吸能力（使用具有单个或多个电子传递系统输入的通透纤维评估）、柠檬酸合酶活性（线粒体体积的标志物）、抽搐力产生和肌肉抗疲劳能力均增加。这些变化不能很好地用肌肉纤维类型组成的变化来解释。然而，与低海拔小鼠相比，高海拔小鼠的膈肌功能存在一些差异。需要更深程度的低氧（9 kPa 与 12 kPa）才能引起高海拔者线粒体呼吸率的增加。与低海拔者明显增加相反，慢性低氧不会增加通透性纤维中活性氧的释放。总的来说，高海拔小鼠的膈肌具有更高的毛细血管长度密度，对刺激的反应力更小，放松时间更短。后者与高海拔小鼠膈肌中肌浆网 Ca2+-ATP 酶（SERCA）活性的增加有关。
总的来说，我们的工作表明，暴露于慢性低氧会增加膈肌的线粒体呼吸、产力和抗疲劳能力。然而，许多这些影响都被高海拔原生动物膈肌功能的进化变化所抵消，使得慢性低氧下的高海拔者维持与海平面条件下低海拔者相似的膈肌功能。
