Putnam Robert W, Filosa Jessica A, Ritucci Nicola A
Department of Anatomy and Physiology, Wright State University School of Medicine, 3640 Colonel Glenn Highway, Dayton, OH 45435, USA.
Am J Physiol Cell Physiol. 2004 Dec;287(6):C1493-526. doi: 10.1152/ajpcell.00282.2004.
An increase in CO(2)/H(+) is a major stimulus for increased ventilation and is sensed by specialized brain stem neurons called central chemosensitive neurons. These neurons appear to be spread among numerous brain stem regions, and neurons from different regions have different levels of chemosensitivity. Early studies implicated changes of pH as playing a role in chemosensitive signaling, most likely by inhibiting a K(+) channel, depolarizing chemosensitive neurons, and thereby increasing their firing rate. Considerable progress has been made over the past decade in understanding the cellular mechanisms of chemosensitive signaling using reduced preparations. Recent evidence has pointed to an important role of changes of intracellular pH in the response of central chemosensitive neurons to increased CO(2)/H(+) levels. The signaling mechanisms for chemosensitivity may also involve changes of extracellular pH, intracellular Ca(2+), gap junctions, oxidative stress, glial cells, bicarbonate, CO(2), and neurotransmitters. The normal target for these signals is generally believed to be a K(+) channel, although it is likely that many K(+) channels as well as Ca(2+) channels are involved as targets of chemosensitive signals. The results of studies of cellular signaling in central chemosensitive neurons are compared with results in other CO(2)- and/or H(+)-sensitive cells, including peripheral chemoreceptors (carotid body glomus cells), invertebrate central chemoreceptors, avian intrapulmonary chemoreceptors, acid-sensitive taste receptor cells on the tongue, and pain-sensitive nociceptors. A multiple factors model is proposed for central chemosensitive neurons in which multiple signals that affect multiple ion channel targets result in the final neuronal response to changes in CO(2)/H(+).
二氧化碳/氢离子浓度升高是通气增加的主要刺激因素，由称为中枢化学敏感神经元的特殊脑干神经元感知。这些神经元似乎分布在众多脑干区域，不同区域的神经元具有不同程度的化学敏感性。早期研究表明，pH值变化在化学敏感信号传导中起作用，最有可能是通过抑制钾离子通道、使化学敏感神经元去极化，从而增加其放电频率。在过去十年中，使用简化标本在理解化学敏感信号传导的细胞机制方面取得了相当大的进展。最近的证据表明，细胞内pH值变化在中枢化学敏感神经元对二氧化碳/氢离子浓度升高的反应中起重要作用。化学敏感性的信号传导机制还可能涉及细胞外pH值、细胞内钙离子、缝隙连接、氧化应激、神经胶质细胞、碳酸氢盐、二氧化碳和神经递质的变化。这些信号的正常靶点通常被认为是钾离子通道，尽管很可能许多钾离子通道以及钙离子通道也作为化学敏感信号的靶点参与其中。将中枢化学敏感神经元的细胞信号传导研究结果与其他对二氧化碳和/或氢离子敏感的细胞的结果进行了比较，这些细胞包括外周化学感受器（颈动脉体球细胞）、无脊椎动物中枢化学感受器、鸟类肺内化学感受器、舌头上的酸敏感味觉感受器细胞和疼痛敏感的伤害感受器。针对中枢化学敏感神经元提出了一个多因素模型，其中影响多个离子通道靶点的多个信号导致神经元对二氧化碳/氢离子变化的最终反应。
