Anesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK-1-like background K(+) current.
Anesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK-1-like background K(+) current.
复制标题
DOI：
10.1523/jneurosci.1956-10.2010
复制
发表时间：
2010-07-07
期刊：
影响因子：
--
通讯作者：
Bayliss DA
中科院分区：
文献类型：
--
作者：
Lazarenko RM;Fortuna MG;Shi Y;Mulkey DK;Takakura AC;Moreira TS;Guyenet PG;Bayliss DA
在手术麻醉深度，吸入麻醉剂引起对疼痛刺激的运动反应的丧失（即，制动），其特征在于脊髓运动回路的深度抑制。然而，尽管明显受到抑制，呼吸运动系统在这些相同的条件下继续提供足够的通气。在这里，我们表明，异氟烷导致强大的激活CO2/pH值敏感，Phox 2b表达神经元位于后斜方核（RTN）的啮齿动物脑干，在体外和体内。在Phox 2b-eGFP小鼠的脑干切片中，异氟烷强烈增加了pH敏感性RTN神经元的放电，与当时的pH条件无关。至少有两种离子机制有助于RTN神经元的麻醉激活：Na+依赖性阳离子电流的激活和背景K+电流的抑制。分离的GFP标记的RTN神经元的单细胞RT-PCR分析揭示了THIK-1（K2P13.1）的表达，THIK-1是一种与天然RTN电流共享关键特性的通道（即，吸入性麻醉剂抑制、弱整流、细胞外Na+抑制和pH不敏感性）。异氟烷也增加放电率的RTN化学敏感神经元在麻醉大鼠，再次独立的CO2水平。在这些动物中，异氟烷可短暂增强呼吸系统的活性，这种效应在低水平呼吸驱动下最为突出，主要通过呼吸频率增加介导。这些数据表明，吸入麻醉剂引起RTN神经元的激活，这在呼吸控制中起着重要的综合作用;增强RTN神经元活动所提供的驱动力增加可能部分有助于在固定麻醉条件下维持呼吸运动活动。
At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO2/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of a Na+-dependent cationic current and inhibition of a background K+ current. Single cell RT-PCR analysis of dissociated GFP-labeled RTN neurons revealed expression of THIK-1 (K2P13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na+, and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO2 levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated largely by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.