Department of Physiological Genomics, Biomedical Center, Ludwig-Maximilians-University, Großhaderner Str. 9, D-82152, Planegg-Martinsried, Germany.
Institute for Stem Cell Research, German Research Center for Environmental Health, Helmholtz Centre Munich, Ingolstädter Landstraße 1, D-85764, Neuherberg, Germany.
J Physiol. 2019 Apr;597(7):1993-2006. doi: 10.1113/JP277139. Epub 2019 Feb 13.
Acetylcholine receptors are aggregated in the central regions of intrafusal muscle fibres. Single unit muscle spindle afferent responses from isolated mouse extensor digitorum longus muscle were recorded in the absence of fusimotor input to ramp and hold stretches as well as to sinusoidal vibrations in the presence and absence of the acetylcholine receptor blockers d-tubocurarine and α-bungarotoxin. Proprioceptive afferent responses to both types of stretch were enhanced in the presence of either blocker. Blocking acetylcholine uptake and vesicular acetylcholine release by hemicholinium-3 also enhanced stretch-evoked responses. These results represent the first evidence that acetylcholine receptors negatively modulate muscle spindle responses to stretch. The data support the hypothesis that the sensory nerve terminal is able to release vesicles to fine-tune proprioceptive afferent sensitivity.
Muscle spindles are complex stretch-sensitive mechanoreceptors. They consist of specialized skeletal muscle fibres, called intrafusal fibres, which are innervated in the central (equatorial) region by afferent sensory axons and in both polar regions by efferent γ-motoneurons. Previously it was shown that acetylcholine receptors (AChR) are concentrated in the equatorial region at the contact site between the sensory neuron and the intrafusal muscle fibre. To address the function of these AChRs, single unit sensory afferents were recorded from an isolated mouse extensor digitorum longus muscle in the absence of γ-motoneuron activity. Specifically, we investigated the responses of individual sensory neurons to ramp-and-hold stretches and sinusoidal vibrations before and after the addition of the competitive and non-competitive AChR blockers d-tubocurarine and α-bungarotoxin, respectively. The presence of either drug did not affect the resting action potential discharge frequency. However, the action potential frequencies in response to stretch were increased. In particular, frequencies of the dynamic peak and dynamic index to ramp-and-hold stretches were significantly higher in the presence of either drug. Treatment of muscle spindle afferents with the high-affinity choline transporter antagonist hemicholinium-3 similarly increased muscle spindle afferent firing frequencies during stretch. Moreover, the firing rate during sinusoidal vibration stimuli at low amplitudes was higher in the presence of α-bungarotoxin compared to control spindles also indicating an increased sensitivity to stretch. Collectively these data suggest a modulation of the muscle spindle afferent response to stretch by AChRs in the central region of intrafusal fibres possibly fine-tuning muscle spindle sensitivity.
乙酰胆碱受体聚集在肌梭内纤维的中央区域。在没有梭内肌传入纤维的牵张反射输入的情况下，从分离的小鼠趾长伸肌中记录到单个肌梭传入神经单位的反应，以及在存在和不存在乙酰胆碱受体阻滞剂筒箭毒碱和α-银环蛇毒素的情况下，对斜坡和保持伸展以及正弦振动的反应。在两种阻滞剂的存在下，本体感受传入反应都增强。通过 hemicholinium-3 阻断乙酰胆碱摄取和囊泡乙酰胆碱释放也增强了拉伸引起的反应。这些结果首次证明乙酰胆碱受体负调节肌梭对拉伸的反应。这些数据支持这样的假设，即感觉神经末梢能够释放囊泡来微调本体感受传入的敏感性。
肌梭是复杂的拉伸敏感机械感受器。它们由称为肌梭内纤维的特殊骨骼肌纤维组成，这些纤维在中央（赤道）区域被传入感觉轴突支配，在两个极区被传出γ运动神经元支配。以前的研究表明，乙酰胆碱受体（AChR）在感觉神经元和肌梭内纤维的接触部位集中在赤道区域。为了研究这些 AChR 的功能，从分离的小鼠趾长伸肌中记录了单个单位的感觉传入神经纤维的反应，在没有γ运动神经元活动的情况下。具体来说，我们研究了在分别加入竞争性和非竞争性 AChR 阻滞剂筒箭毒碱和α-银环蛇毒素前后，单个感觉神经元对斜坡和保持伸展以及正弦振动的反应。两种药物的存在都不影响静息动作电位放电频率。然而，对伸展的动作电位频率增加。特别是，在存在两种药物中的任何一种药物时，对斜坡和保持伸展的动态峰和动态指数的动作电位频率明显更高。用高亲和力胆碱转运体拮抗剂 hemicholinium-3 处理肌梭传入纤维同样增加了伸展过程中的肌梭传入纤维放电频率。此外，在低振幅正弦振动刺激下，α-银环蛇毒素存在时的放电率也高于对照肌梭，这也表明对拉伸的敏感性增加。这些数据共同表明，乙酰胆碱受体在肌梭内纤维的中央区域对肌梭传入纤维的反应进行调节，可能是对肌梭敏感性进行微调。
