Idaho State University, Department of Biological Sciences and Dental Sciences, 921 S. 8th Avenue, Stop 8007, Pocatello, Idaho 83209, USA.
J Neurophysiol. 2012 Jan;107(1):257-64. doi: 10.1152/jn.00623.2011. Epub 2011 Oct 19.
Neuronal nicotinic acetylcholine receptors (nAChRs) are expressed on hypoglossal motor neurons (XII MNs) that innervate muscles of the tongue. Activation of XII MN nAChRs evokes depolarizing currents, which are important for regulating the size and stiffness of the upper airway. Although data show that chronic developmental nicotine exposure (DNE) blunts cholinergic neurotransmission in the XII motor nucleus, it is unclear how nAChRs are involved. Therefore, XII MN nAChR desensitization and recovery were examined in tissues from DNE or control pups using a medullary slice preparation and tight-seal whole cell patch-clamp recordings. nAChR-mediated inward currents were evoked by brief pressure pulses of nicotine or the α4β2 nAChR agonist RJR-2403. We found that, regardless of treatment, activatable nAChRs underwent desensitization, but, following DNE, nAChRs exhibited increased desensitization and delayed recovery. Similar results were produced using RJR-2403, showing that DNE influences primarily the α4β2 nAChR subtype. These results show that while some nAChRs preserve their responsiveness to acute nicotine following DNE, they more readily desensitize and recover more slowly from the desensitized state. These data provide new evidence that chronic DNE modulates XII MN nAChR function, and suggests an explanation for the association between DNE and the incidence of central and obstructive apneas.
神经元烟碱型乙酰胆碱受体（nAChRs）表达于舌下运动神经元（XII MNs）上，这些神经元支配着舌头的肌肉。激活 XII MN nAChRs 会引起去极化电流，这对于调节上呼吸道的大小和硬度非常重要。尽管数据表明，慢性发育性尼古丁暴露（DNE）会使 XII 运动核中的胆碱能神经传递变钝，但目前尚不清楚 nAChRs 是如何参与其中的。因此，使用延髓切片制备和紧密封接全细胞膜片钳记录技术，研究了 DNE 或对照幼崽组织中 XII MN nAChR 的脱敏和恢复情况。通过短暂的尼古丁压力脉冲或α4β2 nAChR 激动剂 RJR-2403 来诱发 nAChR 介导的内向电流。我们发现，无论是否接受治疗，可激活的 nAChRs 都会发生脱敏，但在 DNE 后，nAChRs 表现出增强的脱敏和延迟恢复。使用 RJR-2403 也得到了类似的结果，表明 DNE 主要影响α4β2 nAChR 亚型。这些结果表明，虽然一些 nAChRs 在 DNE 后仍能对急性尼古丁保持反应性，但它们更容易脱敏，并且从脱敏状态中恢复得更慢。这些数据为慢性 DNE 调节 XII MN nAChR 功能提供了新的证据，并为 DNE 与中枢性和阻塞性呼吸暂停发生率之间的关联提供了一种解释。
