Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Division of Cell Signaling, National Institute for Physiological Sciences (Exploratory Research Center for Life and Living Systems), National Institutes of Natural Sciences, Okazaki, Aichi, 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Aichi, 444-8787, Japan.
Respir Physiol Neurobiol. 2019 May;263:20-25. doi: 10.1016/j.resp.2019.03.002. Epub 2019 Mar 4.
The role of TRP channels in the ventilatory response to CO was investigated in vivo. To this end, the respiration of unrestrained adult TRPM8-, TRPV1- and TRPV4-channel knockout mice was measured using whole-body plethysmography. Under control conditions and hyperoxic hypercapnia, no difference in respiratory parameters was observed between adult wild-type mice and TRPV1- and TRPV4-channel knockout mice. However, TRPM8-channel knockout mice showed decreased tidal volume under both hypercapnia and resting conditions. In addition, the expression of TRPM8, TRPV1 and TRPV4 mRNAs was detected in EGFP-positive glial cells in the medulla of GFAP promoter-EGFP transgenic mice by real-time PCR. Furthermore, we measured intracellular Ca responses of TRPM8-overexpressing HEK-293 cells to hypercapnic acidosis. Subpopulations of cells that exhibited hypercapnic acidosis-induced Ca response also responded to the application of menthol. These results suggest that TRPM8 partially mediates the ventilatory response to CO via changes in intracellular Ca and is a chemosensing protein that may be involved in detecting endogenous CO production.
本研究旨在探讨瞬时受体电位通道（TRP）在 CO 通气反应中的作用。为此，采用全身呼吸描记法测量了未受约束的成年 TRPM8、TRPV1 和 TRPV4 通道基因敲除小鼠的呼吸情况。在对照条件和高氧高碳酸血症下，成年野生型小鼠与 TRPV1 和 TRPV4 通道基因敲除小鼠的呼吸参数无差异。然而，TRPM8 通道基因敲除小鼠在高碳酸血症和静息状态下潮气量降低。此外，通过实时 PCR 检测了 GFAP 启动子-EGFP 转基因小鼠延髓中 EGFP 阳性神经胶质细胞中 TRPM8、TRPV1 和 TRPV4 mRNA 的表达。此外，我们还测量了 TRPM8 过表达 HEK-293 细胞对高碳酸酸中毒诱导的细胞内 Ca 反应。表现出高碳酸酸中毒诱导 Ca 反应的细胞亚群也对薄荷醇的应用有反应。这些结果表明，TRPM8 通过细胞内 Ca 变化部分介导 CO 的通气反应，是一种化学感受蛋白，可能参与检测内源性 CO 的产生。
