Institute for Integrative Physiology and Center for Systems Biology of O2 Sensing, University of Chicago, Chicago, Illinois, USA.
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Acta Physiol (Oxf). 2022 Oct;236(2):e13851. doi: 10.1111/apha.13851. Epub 2022 Jun 27.
Naked mole rats (NMRs) exhibit blunted hypoxic (HVR) and hypercapnic ventilatory responses (HCVR). The mechanism(s) underlying these responses are largely unknown. We hypothesized that attenuated carotid body (CB) sensitivity to hypoxia and hypercapnia contributes to the near absence of ventilatory responses to hypoxia and CO in NMRs.
We measured ex vivo CB sensory nerve activity, phrenic nerve activity (an estimation of ventilation), and blood gases in urethane-anesthetized NMRs and C57BL/6 mice breathing normoxic, hypoxic, or hypercapnic gases. CB morphology, carbon monoxide, and H S levels were also determined.
Relative to mice, NMRs had blunted CB and HVR. Morphologically, NMRs have larger CBs, which contained more glomus cells than in mice. Furthermore, NMR glomus cells form a dispersed pattern compared to a clustered pattern in mice. Hemeoxygenase (HO)-1 mRNA was elevated in NMR CBs, and an HO inhibitor increased CB sensitivity to hypoxia in NMRs. This increase was blocked by an H S synthesis inhibitor, suggesting that interrupted gas messenger signaling contributes to the blunted CB responses and HVR in NMRs. Regarding hypercapnia, CB and ventilatory responses to CO in NMRs were larger than in mice. Carbonic anhydrase (CA)-2 mRNA is elevated in NMR CBs, and a CA inhibitor blocked the augmented CB response to CO in NMRs, indicating CA activity regulates augmented CB response to CO .
Consistent with our hypothesis, impaired CB responses to hypoxia contribute in part to the blunted HVR in NMRs. Conversely, the HCVR and CB are more sensitive to CO in NMRs.
裸鼹鼠（NMRs）表现出迟钝的低氧（HVR）和高碳酸血症通气反应（HCVR）。这些反应的机制尚不清楚。我们假设颈动脉体（CB）对缺氧和高碳酸血症的敏感性降低，导致 NMR 对缺氧和 CO 几乎没有通气反应。
我们在使用乌拉坦麻醉的 NMR 和 C57BL/6 小鼠中测量了离体 CB 感觉神经活动、膈神经活动（通气的估计）和血气，这些小鼠呼吸正常氧、低氧或高碳酸气体。还确定了 CB 形态、一氧化碳和 H2S 水平。
与小鼠相比，NMR 的 CB 和 HVR 更为迟钝。从形态上看，NMR 的 CB 更大，其中含有比小鼠更多的小球细胞。此外，NMR 小球细胞形成弥散模式，而小鼠中的小球细胞形成簇状模式。HO-1 mRNA 在 NMR CB 中升高，HO 抑制剂增加了 NMR 中 CB 对缺氧的敏感性。这种增加被 H2S 合成抑制剂阻断，表明中断气体信使信号有助于 NMR 中 CB 反应和 HVR 的迟钝。关于高碳酸血症，NMR 中 CB 和对 CO 的通气反应大于小鼠。NMR CB 中的碳酸酐酶（CA）-2 mRNA 升高，CA 抑制剂阻断了 NMR 中 CO 对 CB 反应的增强，表明 CA 活性调节了 CO 对 CB 反应的增强。
与我们的假设一致，CB 对缺氧的反应受损部分导致 NMR 中 HVR 的迟钝。相反，HCVR 和 CB 对 CO 更敏感。
