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Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice

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Abstract

Deer mice, Peromyscusmaniculatus, live at high altitudes where limited O2 represents a challenge to maintaining oxygen delivery to tissues. Previous work has demonstrated that hypoxia acclimation of deer mice and low altitude white-footed mice (P. leucopus) increases the force generating capacity of the diaphragm. The mechanism behind this improved contractile function is not known. Within myocytes, the myofilament plays a critical role in setting the rate and level of force production, and its ability to generate force can change in response to changes in physiological conditions. In the current study, we examined how chronic hypobaric hypoxia exposure of deer mice and white-footed mice influences the Ca2+ activation of force generation by skinned diaphragmatic myofilaments, and the phosphorylation of myofilament proteins. Results demonstrate that myofilament force production, and the Ca2+ sensitivity of force generation, were not impacted by acclimation to hypobaric hypoxia, and did not differ between preparations from the two species. The cooperativity of the force-pCa relationship, and the maximal rate of force generation were also the same in the preparations from both species, and not impacted by acclimation. Finally, the relative phosphorylation of TnT, and MLC was lower in deer mice than white-footed mice, but was not affected by acclimation. These results indicate that species differences in diaphragm function, and the increase in force production with hypoxia acclimation, are not due to differences, or changes, in myofilament function. However, it appears that diaphragmatic myofilament function in these species is not affected by chronic hypobaric hypoxia exposure.

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Acknowledgements

The authors thank Nicole Pranckevicius for assisting with sample collections.

Funding

YD was supported by an Undergraduate Student Research Award from the Natural Sciences and Engineering Research Council (NSERC) of Canada. GRS is supported by an NSERC Discovery Grant and the Canada Research Chairs Program. TEG is supported by an NSERC Discovery Grant and an NSERC Discovery Accelerator Supplement. Equipment used in this study was purchased with funds from the Canadian Foundation for Innovation, and the Ontario Ministry of Research and Innovation.

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  1. Department of Integrative Biology, University of Guelph, Guelph, ON, N1G-2W1, Canada

    Y. Ding & Todd E. Gillis

  2. Department of Biology, McMaster University, Hamilton, ON, Canada

    S. A. Lyons & G. R. Scott

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  1. Y. Ding
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  2. S. A. Lyons
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Correspondence to Todd E. Gillis.

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Ding, Y., Lyons, S.A., Scott, G.R. et al. Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice. J Comp Physiol B 189, 489–499 (2019). https://doi.org/10.1007/s00360-019-01224-w

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