Neverova Natalia V, Saywell Shane A, Nashold Lisa J, Mitchell Gordon S, Feldman Jack L
Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095-1763, USA.
J Neurosci. 2007 Apr 18;27(16):4435-42. doi: 10.1523/JNEUROSCI.2803-06.2007.
In vitro long-term facilitation (ivLTF) is a novel form of activity-independent postsynaptic enhancement of AMPA receptor function in hypoglossal (XII) motoneurons that can be induced by intermittent activation of 5-HT2 receptors. In vivo respiratory long-term facilitation (LTF) is characterized by a persistent 5-HT2 receptor-dependent increase in respiratory motor output or ventilation after episodic exposures to hypoxia in adult rats. Here, we demonstrate that ivLTF can also be induced by episodic but not continuous stimulation of alpha1-adrenergic receptors that requires protein kinase C (PKC), but not PKA (protein kinase A), activation. Additionally, we show that in vivo respiratory LTF is also alpha1-adrenergic receptor dependent. We suggest that, in vivo, concurrent episodic activation of 5-HT2 and alpha1-adrenergic receptors is necessary to produce long-lasting changes in the excitability of respiratory motoneurons, possibly involving PKC activation via the G alpha(q)-PLC (phospholipase C) signaling pathway common to both receptor subtypes. Such plasticity of XII motor output may increase upper airway muscle (innervated by XII nerve) tone and improve the likelihood that airway patency will be maintained. Elucidating the mechanism underlying LTF can be of clinical importance to the patients suffering from sleep-disordered breathing.
体外长期易化（ivLTF）是舌下（XII）运动神经元中一种新型的、不依赖活动的AMPA受体功能的突触后增强形式，可由5-HT2受体的间歇性激活诱导产生。体内呼吸长期易化（LTF）的特征是成年大鼠在间歇性暴露于低氧环境后，呼吸运动输出或通气持续出现依赖5-HT2受体的增加。在此，我们证明ivLTF也可由间歇性而非持续性刺激α1-肾上腺素能受体诱导产生，这一过程需要蛋白激酶C（PKC）而非蛋白激酶A（PKA）的激活。此外，我们还表明体内呼吸LTF也依赖α1-肾上腺素能受体。我们认为，在体内，5-HT2和α1-肾上腺素能受体的同时间歇性激活对于呼吸运动神经元兴奋性产生持久变化是必要的，这可能涉及通过两种受体亚型共有的Gα(q)-磷脂酶C（PLC）信号通路激活PKC。XII运动输出的这种可塑性可能会增加上气道肌肉（由XII神经支配）的张力，并提高维持气道通畅的可能性。阐明LTF的潜在机制对于患有睡眠呼吸障碍的患者可能具有临床重要性。
