Zoophysiology, Department of Bioscience, Aarhus University, 8000 Aarhus C, Denmark.
School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.
Comp Biochem Physiol A Mol Integr Physiol. 2016 May;195:10-4. doi: 10.1016/j.cbpa.2016.01.018. Epub 2016 Jan 22.
An important means of physiological adaptation to environmental hypoxia is an increased oxygen (O2) affinity of the hemoglobin (Hb) that can help secure high O2 saturation of arterial blood. However, the trade-off associated with a high Hb-O2 affinity is that it can compromise O2 unloading in the systemic capillaries. High-altitude deer mice (Peromyscus maniculatus) have evolved an increased Hb-O2 affinity relative to lowland conspecifics, but it is not known whether they have also evolved compensatory mechanisms to facilitate O2 unloading to respiring tissues. Here we investigate the effects of pH (Bohr effect) and temperature on the O2-affinity of high- and low-altitude deer mouse Hb variants, as these properties can potentially facilitate O2 unloading to metabolizing tissues. Our experiments revealed that Bohr factors for the high- and low-altitude Hb variants are very similar in spite of the differences in O2-affinity. The Bohr factors of deer mouse Hbs are also comparable to those of other mammalian Hbs. In contrast, the high- and low-altitude variants of deer mouse Hb exhibited similarly low temperature sensitivities that were independent of red blood cell anionic cofactors, suggesting an appreciable endothermic allosteric transition upon oxygenation. In conclusion, high-altitude deer mice have evolved an adaptive increase in Hb-O2 affinity, but this is not associated with compensatory changes in sensitivity to changes in pH or temperature. Instead, it appears that the elevated Hb-O2 affinity in high-altitude deer mice is compensated by an associated increase in the tissue diffusion capacity of O2 (via increased muscle capillarization), which promotes O2 unloading.
生理适应环境缺氧的一个重要手段是增加血红蛋白（Hb）对氧气（O2）的亲和力，这有助于确保动脉血液的高 O2 饱和度。然而，与高 Hb-O2 亲和力相关的权衡是，它可能会损害系统毛细血管中的 O2 释放。高海拔鹿鼠（Peromyscus maniculatus）相对于低海拔同种动物进化出了更高的 Hb-O2 亲和力，但目前尚不清楚它们是否也进化出了补偿机制来促进 O2 向呼吸组织释放。在这里，我们研究了 pH（波尔效应）和温度对高海拔和低海拔鹿鼠 Hb 变体 O2 亲和力的影响，因为这些特性可能有助于向代谢组织释放 O2。我们的实验表明，尽管 O2 亲和力存在差异，但高海拔和低海拔 Hb 变体的波尔因子非常相似。鹿鼠 Hbs 的波尔因子也与其他哺乳动物 Hbs 的波尔因子相当。相比之下，鹿鼠 Hb 的高海拔和低海拔变体表现出相似的低温度敏感性，这种敏感性独立于红细胞阴离子辅助因子，这表明在氧合时存在可观的吸热变构转变。总之，高海拔鹿鼠已经进化出 Hb-O2 亲和力的适应性增加，但这与对 pH 或温度变化的敏感性的补偿性变化无关。相反，高海拔鹿鼠中升高的 Hb-O2 亲和力似乎通过 O2 的组织扩散能力（通过增加肌肉毛细血管化）的增加得到了补偿，这促进了 O2 的释放。
