Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
J Physiol. 2021 Mar;599(6):1917-1932. doi: 10.1113/JP280788. Epub 2021 Feb 15.
Dysfunctions in the hypoglossal control of tongue extrinsic muscles are implicated in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH), an important feature of OSA syndrome, produces deleterious effects on the motor control of oropharyngeal resistance, but whether the hypoglossal motoneurones innervating the tongue extrinsic muscles are affected by CIH is unknown. We show that CIH enhanced the respiratory-related activity of rat hypoglossal nerve innervating the protrudor and retractor tongue extrinsic muscles. Intracellular recordings revealed increases in respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones after CIH. CIH also increased their intrinsic excitability, depolarised resting membrane potential and reduced K -dominated leak conductance. CIH affected the breathing-related synaptic control and intrinsic electrophysiological properties of protrudor and retractor hypoglossal motoneurones to optimise the neural control of oropharyngeal function.
Inspiratory-related tongue movements and oropharyngeal motor actions are controlled mainly by the protrudor and retractor extrinsic tongue muscles, which are innervated by the hypoglossal motoneurones. Chronic intermittent hypoxia (CIH), an important feature of obstructive sleep apnoea syndrome, produces detrimental effects on the contractile function of the tongue extrinsic muscles and the medullary inspiratory network of rodents. However, the impact of the CIH on the electrophysiological properties of protrudor and retractor hypoglossal motoneurones has not been described before. Using nerves and intracellular recordings in in situ preparation of rats (5 weeks old), we tested the hypothesis that CIH (FiO of 0.06, SaO 74%, during 30-40 s, every 9 min, 8 h/day for 10 days) increases the intrinsic excitability of protrudor and retractor motoneurones from the hypoglossal motor nucleus of rats. Recordings of hypoglossal nerve, before its bifurcation to innervate the tongue protrudor and retractor muscles, revealed that CIH enhances its pre-inspiratory, simultaneously with the presence of active expiration, and inspiratory activities. These changes were mediated by increases in the respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones. Besides, CIH increases their intrinsic excitability and depolarises resting membrane potential by reducing a K -dominated leak conductance. In conclusion, CIH enhances the respiratory-related neural control of oropharyngeal function of rats by increasing the synaptic excitation, intrinsic excitability, and reducing leak conductance in both protrudor and retractor hypoglossal motoneurones. We propose that these network and cellular changes are important to optimise the oropharyngeal resistance in conditions related to intermittent hypoxia.
舌下神经对外展肌的控制功能障碍与阻塞性睡眠呼吸暂停（OSA）综合征有关。慢性间歇性低氧（CIH）是 OSA 综合征的一个重要特征，对口咽阻力的运动控制产生有害影响，但舌下神经支配舌外展肌的运动神经元是否受到 CIH 的影响尚不清楚。我们发现 CIH 增强了支配伸舌和缩舌外展肌的大鼠舌下神经的呼吸相关活动。细胞内记录显示，CIH 后，吸气性伸舌和缩舌舌下运动神经元的呼吸相关放电频率和突触兴奋性增加。CIH 还增加了它们的内在兴奋性，使静息膜电位去极化，并减少 K 主导的漏导。CIH 影响了伸舌和缩舌舌下运动神经元的呼吸相关突触控制和内在电生理特性，以优化口咽功能的神经控制。
吸气相关的舌运动和口咽运动主要由伸舌和缩舌外展舌肌控制，这些肌肉由舌下运动神经元支配。慢性间歇性低氧（CIH）是阻塞性睡眠呼吸暂停综合征的一个重要特征，对舌外展肌的收缩功能和啮齿动物延髓吸气网络产生有害影响。然而，CIH 对伸舌和缩舌舌下运动神经元的电生理特性的影响以前尚未描述过。我们在大鼠原位准备（5 周龄）中使用神经和细胞内记录来测试 CIH（FiO 为 0.06，SaO 为 74%，持续 30-40 秒，每 9 分钟一次，每天 8 小时，持续 10 天）增加大鼠舌下运动核中伸舌和缩舌运动神经元内在兴奋性的假设。在舌下神经分叉之前记录其活动，以支配舌伸肌和缩肌，结果表明 CIH 增强了其预吸气活动，同时伴随着主动呼气，并增强了吸气活动。这些变化是通过增加吸气性伸舌和缩舌舌下运动神经元的呼吸相关放电频率和突触兴奋性来介导的。此外，CIH 通过降低 K 主导的漏导来增加其内在兴奋性并去极化静息膜电位。总之，CIH 通过增加伸舌和缩舌舌下运动神经元的突触兴奋性、内在兴奋性和减少漏导，增强了大鼠口咽功能的呼吸相关神经控制。我们提出，这些网络和细胞变化对于优化间歇性低氧相关条件下的口咽阻力很重要。
