Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep
Identification of the Mechanism Mediating Genioglossus Muscle Suppression in REM Sleep
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DOI：
10.1164/rccm.201209-1654oc
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发表时间：
2013-02-01
影响因子：
24.7
通讯作者：
Horner, Richard L.
中科院分区：
文献类型：
--
作者：
Grace, Kevin P.;Hughes, Stuart W.;Horner, Richard L.
原理：咽运动神经元的抑制伴随着REM睡眠，是人类通气不足和阻塞性睡眠呼吸暂停的原因。一种解释认为，神经递质甘氨酸和γ-氨基丁酸负责REM睡眠运动抑制。然而，该机制在颅运动核阻滞增加运动活动在所有的睡眠觉醒状态，至少在REM睡眠，反对它作为一个主要的机制REM睡眠咽运动inhibit 1 n.Objectives：要确定REM睡眠抑制的机制在舌下神经motorpool.Methods：Genioglossus和膈肌活动记录在34只大鼠在整个睡眠觉醒状态。微透析探针植入到舌下神经motorpool.Measurements和主要结果：在这里，我们表明，毒蕈碱受体拮抗作用在舌下神经运动池防止整个REM睡眠的颏舌肌活动的抑制，同样，与G-蛋白偶联内向整流钾（G IRK）通道阻滞。重要的是，这些干预措施的颏舌肌激活作用在REM睡眠中最大，在其他睡眠清醒状态中最小或通常不存在。最后，我们发现，毒蕈碱抑制颏舌肌的功能与GIRK通道activation.Conclusions：我们确定了一个强大的胆碱能GIRK通道的机制，在舌下神经运动池，有其最大的抑制作用，在REM睡眠和最小或没有影响，在其他睡眠清醒状态。这一机制是在咽运动池中REM睡眠抑制的主要原因，咽运动池对有效呼吸至关重要。
Rationale: Inhibition of pharyngeal motoneurons accompanies REM sleep and is a cause of hypoventilation and obstructive sleep apnea in humans. One explanation posits that the neurotransmitters glycine and gamma-aminobutyric acid are responsible for REM sleep motor inhibition. However, blockade of that mechanism at cranial motor nuclei increases motor activity in all sleep wake states, and least of all in REM sleep; arguing against it as a major mechanism of REM sleep pharyngeal motor inhibition.Objectives: To identify the mechanism of REM sleep inhibition at the hypoglossal motor pool.Methods: Genioglossus and diaphragm activities were recorded in 34 rats across sleep wake states. Microdialysis probes were implanted into the hypoglossal motor pool.Measurements and Main Results: Here we show that muscarinic receptor antagonism at the hypoglossal motor pool prevents the inhibition of genioglossus activity throughout REM sleep; likewise, with G-protein-coupled inwardly rectifying potassium (G IRK) channel blockade. Importantly, the genioglossus activating effects of these interventions were largest in REM sleep and minimal or often absent in other sleep wake states. Finally, we showed that muscarinic inhibition of the genioglossus is functionally linked to GIRK channel activation.Conclusions: We identify a powerful cholinergic-GIRK channel mechanism operating at the hypoglossal motor pool that has its largest inhibitory influence in REM sleep and minimal or no effects in other sleep wake states. This mechanism is the major cause of REM sleep inhibition at a pharyngeal motor pool critical for effective breathing.