Nichols Nicole L, Powell Frank L, Dean Jay B, Putnam Robert W
Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, United States of America.
Division of Physiology, University of California San Diego School of Medicine, La Jolla, California, United States of America.
PLoS One. 2014 Feb 7;9(2):e88161. doi: 10.1371/journal.pone.0088161. eCollection 2014.
NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+)-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.
与P物质结合的NK1受体存在于大多数脑干区域，这些区域含有对二氧化碳/氢离子敏感的神经元，它们在中枢化学感受中发挥作用。然而，P物质对这些区域神经元化学感受反应的影响尚未得到研究。缺氧会增加终止于延髓尾端孤束核（NTS）的外周传入神经释放P物质。在此，我们研究了P物质对来自对照成年大鼠和慢性缺氧适应（CHx）成年大鼠的孤束复合体（SC：NTS和背运动核）神经元化学感受反应的影响。我们使用盲法全细胞膜片钳技术和荧光成像显微镜同时测量对照成年大鼠和CHx成年大鼠SC神经元的细胞内pH值以及对高碳酸血症酸中毒的电反应。P物质显著提高了对照大鼠和CHx大鼠SC神经元的基础放电率，尽管CHx大鼠的增加幅度较小。然而，P物质并未影响两组大鼠SC神经元的化学感受反应。总之，我们发现P物质在调节SC神经元的基础放电率中发挥作用，但对CHx成年大鼠的SC神经元而言，这种作用的幅度较小，这意味着NK1受体在CHx成年大鼠中可能下调。P物质似乎在调节对照成年大鼠或CHx成年大鼠SC神经元对高碳酸血症酸中毒的放电率反应中不起作用。
