Spontaneous Tonic Activity Revealed in Rat Soleus Muscle by CLP290, a Novel Spinal Cord Potassium-Chloride Cotransporter Activator, during Hindlimb Suspension

Pub Date : 2024-08-29 DOI:10.1134/s002209302404032x
V. E. Kalashnikov, K. V. Sergeeva, O. V. Turtikova, S. A. Tyganov, T. M. Mirzoev, B. S. Shenkman
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Abstract

The electromyographic activity of the soleus muscle is a reliable indicator of its functional status. Support unloading causes an immediate cessation of electrical activity of the soleus muscle, which resumes upon restoration of the support load. Prolonged support unloading, however, results in the emergence of spontaneous electrical activity of the soleus muscle. Previous research has established a correlation between this activity and the presence of the potassium-chloride cotransporter (KCC2) on the membranes of spinal cord motor neurons. It has also been demonstrated that the administration of the KCC2 activator prochlorperazine can eliminate spontaneous soleus muscle activity. Here, we aimed to investigate the effect of CLP290, an alternative KCC2 activator, on the spontaneous tonic activity of the rat soleus muscle. The results indicated that daily administration of CLP290 to rats during a 14-day period of hindlimb suspension prevented the reduction in KCC2 levels in lumbar spinal cord motor neurons and the increase in soleus muscle spontaneous tonic activity. Notably, there were no significant differences in the cross-sectional area of slow-type fibers between the antiorthostatic suspension groups with and without CLP290 administration.

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一种新型脊髓钾氯化物共转运体激活剂 CLP290 在后肢悬吊过程中揭示的大鼠足底肌肉自发强直活动
摘要比目鱼肌的肌电活动是其功能状态的可靠指标。支撑物卸载会导致比目鱼肌电活动立即停止,恢复支撑负荷后又会恢复。然而,长时间的支撑负荷会导致比目鱼肌出现自发的电活动。以前的研究已经证实,这种活动与脊髓运动神经元膜上存在的钾氯转运体(KCC2)有关。在此,我们旨在研究替代 KCC2 激活剂 CLP290 对比目鱼肌自发性强直活动的影响。结果表明,大鼠在为期 14 天的后肢悬吊期间每天服用 CLP290 可防止腰脊髓运动神经元中 KCC2 水平的降低和比目鱼肌自发强直活动的增加。值得注意的是,在服用和未服用 CLP290 的抗失稳悬吊组之间,慢型纤维的横截面积没有明显差异。
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