Tsuzawa K, Yazawa I, Shakuo T, Ikeda K, Kawakami K, Onimaru H
Department of Physiology, Showa University School of Medicine, Tokyo 142-8555, Japan.
Department of Anatomy, Showa University School of Medicine, Tokyo 142-8555, Japan.
Neuroscience. 2015 Feb 12;286:404-11. doi: 10.1016/j.neuroscience.2014.12.006. Epub 2014 Dec 12.
The significance of Na/K-ATPase on respiratory rhythm generation is not well understood. We investigated the effects of the Na/K-ATPase blocker, ouabain, on respiratory rhythm. Experiments were performed with brainstem-spinal cord preparation from 0 to 3-day-old Wistar rats and with decerebrate and arterially perfused in situ preparation from juvenile rats (postnatal day 11-13). Newborn rat preparations were superfused at a rate of 3.0 ml/min with artificial cerebrospinal fluid, equilibrated with 95% O2 and 5% CO2, pH 7.4, at 26-27 °C. Inspiratory activity was monitored from the fourth cervical ventral root (C4). Application of ouabain (15-20 min) resulted in a dose-dependent increase in the burst rate of C4 inspiratory activity. After washout, the burst rate further increased to reach quasi-maximum values under each condition (e.g. 183% of control in 1 μM, 253% in 10 μM, and 303% in 20 μM at 30 min washout). Inspiratory or pre-inspiratory neurons in the rostral ventrolateral medulla were depolarized. We obtained similar results (i.e. increased phrenic burst rate) in an in situ perfused preparation of juvenile rats. Genes encoding the Na/K-ATPase α subunit were expressed in the region of the parafacial respiratory group (pFRG) in neonatal rats, suggesting that cells (neurons and/or glias) in the pFRG were one of the targets of ouabain. We concluded that Na/K-ATPase activity could be an important factor in respiratory rhythm modulation.
钠钾ATP酶对呼吸节律产生的意义尚未完全明确。我们研究了钠钾ATP酶阻滞剂哇巴因对呼吸节律的影响。实验采用0至3日龄Wistar大鼠的脑干脊髓标本，以及幼鼠（出生后第11至13天）的去大脑并原位动脉灌注标本。新生大鼠标本以3.0毫升/分钟的速度用人工脑脊液进行灌流，该人工脑脊液在26 - 27℃下用95%氧气和5%二氧化碳平衡，pH值为7.4。从第四颈段腹根（C4）监测吸气活动。应用哇巴因（15 - 20分钟）导致C4吸气活动的爆发频率呈剂量依赖性增加。洗脱后，爆发频率进一步增加，在每种条件下达到近似最大值（例如，在洗脱30分钟时，1微摩尔浓度下为对照的183%，10微摩尔浓度下为253%，20微摩尔浓度下为303%）。延髓头端腹外侧的吸气或吸气前神经元发生去极化。在幼鼠的原位灌注标本中我们也得到了类似结果（即膈神经爆发频率增加）。编码钠钾ATP酶α亚基的基因在新生大鼠的面神经旁呼吸组（pFRG）区域表达，这表明pFRG中的细胞（神经元和/或神经胶质细胞）是哇巴因的作用靶点之一。我们得出结论，钠钾ATP酶活性可能是呼吸节律调节中的一个重要因素。
