Release of ATP in the ventral medulla during hypoxia in rats: Role in hypoxic ventilatory response
Release of ATP in the ventral medulla during hypoxia in rats: Role in hypoxic ventilatory response
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DOI：
10.1523/jneurosci.3763-04.2005
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发表时间：
2005-02-02
影响因子：
5.3
通讯作者：
Spyer, KM
中科院分区：
文献类型：
--
作者：
Gourine, AV;Llaudet, E;Spyer, KM
ATP门控离子通道的P2X(2)受体亚基由腹侧呼吸柱中生理鉴定的呼吸神经元表达，暗示ATP参与呼吸活动的控制。我们现在发现，在低氧期间，延髓腹外侧区(VLM)中的ATP释放在大鼠的低氧呼吸反应中起着重要的作用。通过使用新型电流型生物传感器实时测量延髓腹侧表面的ATP释放量，我们发现低氧(10%O-2；5min)可显著增加延髓腹侧表面的ATP浓度(类似于3um)。这种ATP的释放发生在呼吸活动开始增强之后，但与后来缺氧引起的呼吸节律减慢相吻合。在周围化学神经支配的动物(迷走神经、主动脉和颈动脉窦神经切断)缺氧时，延髓腹侧表面也释放了ATP。通过使用大鼠延髓的水平切片，我们发现，在低氧期间，ATP在整个VLM中与腹侧呼吸柱相对应的位置产生。阻断VLm中的三磷酸腺苷受体(微量注射P2受体拮抗剂pyridoxal-5‘-phosphate-6-azophenyl-2’，4‘-disulphonic酸；100um)可增强缺氧引起的呼吸节律的继发性减慢。我们的发现表明，腹侧呼吸柱中释放的ATP参与了低氧引起的呼吸减慢时呼吸活动的维持。这些数据表明，ATP介导的嘌呤能信号在控制呼吸活动的髓质机制中具有新的功能作用。
P2X(2) receptor subunits of the ATP-gated ion channels are expressed by physiologically identified respiratory neurons in the ventral respiratory column, implicating ATP in the control of respiratory activity. We now show that, during hypoxia, release of ATP in the ventrolateral medulla (VLM) plays an important role in the hypoxic ventilatory response in rats. By measuring ATP release in real time at the ventral surface of the medulla with novel amperometric biosensors, we found that hypoxia (10% O-2; 5 min) induced a marked increase in the concentration of ATP (similar to3 muM). This ATP release occurred after the initiation of enhanced respiratory activity but coincided with the later hypoxia-induced slowing of the respiratory rhythm. ATP was also released at the ventral surface of the medulla during hypoxia in peripherally chemodenervated animals ( vagi, aortic, and carotid sinus nerve sectioned). By using horizontal slices of the rat medulla, we found that, during hypoxia, ATP is produced throughout the VLM in the locations corresponding to the ventral respiratory column. Blockade of ATP receptors in the VLM( microinjection of P2 receptor antagonist pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid; 100 muM) augmented the hypoxia-induced secondary slowing of the respiratory rhythm. Our findings suggest that ATP released within the ventral respiratory column is involved in maintenance of the respiratory activity in conditions when hypoxia-induced slowing of respiration occurs. These data illustrate a new functional role for ATP-mediated purinergic signaling in the medullary mechanisms controlling respiratory activity.