Peterson Rochelle A, König Christine, Zimmermann Katharina, Barry Christine M, Wiklendt Lukasz, Brookes Simon J H
Neurogastroentrology Laboratory, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia.
Klinik für Anästhesiologie am Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Front Cell Neurosci. 2020 Aug 6;14:215. doi: 10.3389/fncel.2020.00215. eCollection 2020.
A class of Group III muscle afferent neurons has branching sensory terminals in the connective tissue between layers of mouse abdominal muscles ("CT3 muscle afferents"). These sensory endings are both mechanosensitive and metabosensitive. In the present study, responses of CT3 afferents to lactate ions and changes in temperature were recorded. Raising muscle temperature from 32.7°C to 37°C had no consistent effects on CT3 afferent basal firing rate or responses to either von Frey hair stimulation or to an applied load. Superfusion with lactate ions (15 mM, pH 7.4) was associated with an increase in firing from 6 ± 0.7 Hz to 11.7 ± 6.7 Hz (14 units, = 13, < 0.05, = 0.0484) but with considerable variability in the nature and latency of response. Reducing the concentration of extracellular divalent cations, which mimicked the chelating effects of lactate, did not increase firing. Raised concentrations of divalent cations (to compensate for chelation) did not block excitatory effects of lactate on CT3 afferents, suggesting that effects ASIC3 were not involved. Messenger RNA for the G-protein coupled receptor, hydroxyl carboxylic acid receptor 1 (HCAR1) was detected in dorsal root ganglia and HCAR1-like immunoreactivity was present in spinal afferent nerve cell bodies retrogradely labeled from mouse abdominal muscles. HCAR1-like immunoreactivity was also present in axons in mouse abdominal muscles. This raises the possibility that some effects of lactate on group III muscle afferents may be mediated by HCAR1.
一类Ⅲ组肌肉传入神经元在小鼠腹肌各层之间的结缔组织中有分支感觉末梢(“CT3肌肉传入纤维”)。这些感觉末梢既对机械敏感,也对代谢敏感。在本研究中,记录了CT3传入纤维对乳酸离子和温度变化的反应。将肌肉温度从32.7℃升高到37℃对CT3传入纤维的基础放电率或对冯·弗里刺激或施加负荷的反应均无一致影响。用乳酸离子(15 mM,pH 7.4)进行灌流时,放电频率从6±0.7 Hz增加到11.7±6.7 Hz(14个单位,= 13,<0.05,= 0.0484),但反应的性质和潜伏期存在相当大的变异性。降低细胞外二价阳离子浓度(模拟乳酸的螯合作用)并未增加放电。提高二价阳离子浓度(以补偿螯合作用)并未阻断乳酸对CT3传入纤维的兴奋作用,表明不涉及ASIC3的作用。在背根神经节中检测到G蛋白偶联受体羟基羧酸受体1(HCAR1)的信使核糖核酸,并且在从小鼠腹肌逆行标记的脊髓传入神经细胞体中存在HCAR1样免疫反应性。HCAR1样免疫反应性也存在于小鼠腹肌的轴突中。这增加了乳酸对Ⅲ组肌肉传入纤维的某些作用可能由HCAR1介导的可能性。