Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota, United States.
Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, United States.
J Appl Physiol (1985). 2023 Jun 1;134(6):1332-1340. doi: 10.1152/japplphysiol.00021.2023. Epub 2023 Apr 6.
Neuromotor control of diaphragm muscle (DIAm) motor units is dependent on an orderly size-dependent recruitment of phrenic motor neurons (PhMNs). Slow (type S) and fast, fatigue resistant (type FR) DIAm motor units, which are frequently recruited to sustain ventilation, comprise smaller PhMNs that innervate type I and IIa DIAm fibers. More fatigable fast (type FF) motor units, which are infrequently recruited for higher force, expulsive behaviors, comprise larger PhMNs that innervate more type IIx/IIb DIAm fibers. We hypothesize that due to the more frequent activation and thus higher energy demand of type S and FR motor units, the mitochondrial volume density (MVD) of smaller PhMNs is greater compared with larger PhMNs. In eight adult (6 mo old) Fischer 344 rats, PhMNs were identified via intrapleural injection of Alexa488-conjugated cholera toxin B (CTB). Following retrograde CTB labeling, mitochondria in PhMNs were labeled by transdural infusion of MitoTracker Red. PhMNs and mitochondria were imaged using multichannel confocal microscopy using a ×60 oil objective. Following optical sectioning and three-dimensional (3-D) rendering, PhMNs and mitochondria were analyzed volumetrically using Nikon Elements software. Analysis of MVD in somal and dendritic compartments was stratified by PhMN somal surface area. Smaller PhMNs (likely S and FR units) had greater somal MVDs compared with larger PhMNs (likely FF units). By contrast, proximal dendrites or larger PhMNs had higher MVD compared with dendrites of smaller PhMNs. We conclude that more active smaller PhMNs have a higher mitochondrial volume density to support their higher energy demand in sustaining ventilation. Type S and FR motor units, comprising smaller phrenic motor neurons (PhMNs) are regularly activated to perform indefatigable ventilatory requirements. By contrast, type FF motor units, comprising larger PhMNs, are infrequently activated to perform expulsive straining and airway defense maneuvers. This difference in activation history is mirrored in the mitochondrial volume density (MVD), with smaller PhMNs having higher MVD than larger PhMNs. In proximal dendrites, this trend was reversed, with larger PhMNs having higher MVD than smaller PhMNs, likely due to the maintenance requirements for the larger dendritic arbor of FF PhMNs.
膈肌(DIAm)运动单位的神经运动控制依赖于有序的、与大小相关的膈神经运动神经元(PhMNs)募集。经常募集来维持通气的慢(S 型)和快速、抗疲劳(FR)DIAm 运动单位,由支配 I 型和 IIa 型 DIAm 纤维的较小 PhMNs 组成。募集频率较低、用于更高力、排出行为的易疲劳快速(FF)运动单位,由支配更多的 IIx/IIb 型 DIAm 纤维的较大 PhMNs 组成。我们假设,由于 S 型和 FR 运动单位的激活更为频繁,因此能量需求更高,较小 PhMNs 的线粒体体积密度(MVD)大于较大 PhMNs。在 8 只成年(6 月龄)Fischer 344 大鼠中,通过胸腔内注射 Alexa488 缀合霍乱毒素 B(CTB)来识别 PhMNs。在逆行 CTB 标记后,通过硬膜内输注 MitoTracker Red 标记 PhMNs 中的线粒体。使用 ×60 油浸物镜的多通道共聚焦显微镜对 PhMNs 和线粒体进行成像。光学切片和三维(3-D)渲染后,使用 Nikon Elements 软件对 PhMNs 和线粒体进行体积分析。根据 PhMN 体表面积对体和树突区的 MVD 进行分层分析。与较大的 PhMNs(可能是 FF 单位)相比,较小的 PhMNs(可能是 S 和 FR 单位)具有更大的体 MVD。相比之下,与较小 PhMNs 的树突相比,近端树突或较大的 PhMNs 具有更高的 MVD。我们得出结论,更活跃的较小 PhMNs 具有更高的线粒体体积密度,以支持其维持通气的更高能量需求。由较小的膈神经运动神经元(PhMNs)组成的 S 型和 FR 运动单位经常被激活以完成不知疲倦的通气需求。相比之下,由较大的 PhMNs 组成的 FF 运动单位很少被激活以进行排出性紧张和气道防御动作。这种激活历史的差异反映在线粒体体积密度(MVD)中,较小的 PhMNs 比较大的 PhMNs 具有更高的 MVD。在近端树突中,这种趋势发生了逆转,较大的 PhMNs 比较小的 PhMNs 具有更高的 MVD,这可能是由于 FF PhMNs 较大的树突分支需要维持。