An investigation of the spontaneous tonic activity of the rat soleus muscle following hindlimb suspension, with a focus on the effects of CLP290, a novel activator of the spinal cord potassium-chloride co-transporter

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Abstract

The electromyographic activity of the soleus muscle is a reliable indicator of its functional status. Unloading of support causes an immediate cessation of electrical activity in the soleus muscle, which resumes upon restoration of the support load. Prolonged support unloading, however, results in the emergence of spontaneous electrical activity in 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. Additionally, it has been demonstrated that the introduction of the KCC2 activator prochlorperazine can eliminate spontaneous muscle activity. This study aimed to investigate the impact 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 the motor neurons of the lumbar spinal cord and the increase in spontaneous tonic activity in the soleus muscle. 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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About the authors

V. E. Kalashnikov

Institute of Biomedical Problems, Russian Academy of Sciences

Author for correspondence.
Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

K. V. Sergeeva

Institute of Biomedical Problems, Russian Academy of Sciences

Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

O. V. Turtikova

Institute of Biomedical Problems, Russian Academy of Sciences

Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

S. A. Tyganov

Institute of Biomedical Problems, Russian Academy of Sciences

Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

T. M. Mirzoev

Institute of Biomedical Problems, Russian Academy of Sciences

Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

B. S. Shenkman

Institute of Biomedical Problems, Russian Academy of Sciences

Email: vitaliy.kalasxnikov@yandex.ru
Russian Federation, Moscow

References

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Supplementary files

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2. Fig. 1. Dynamics of integrated EMG activity of the soleus muscle during 14-day antiorthostatic suspension with and without administration of CLP290. * statistically significant between groups with and without administration of the drug (p < 0.05).

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3. Fig. 2. Typical patterns of EMG activity of the soleus muscle before antiorthostatic suspension (C) and during 14-day suspension (1–14HS) in rats without and with CLP290 administration.

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4. Fig. 3. Median frequency of EMG activity of the soleus muscle during 14-day antiorthostatic suspension with and without administration of CLP290.

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5. Fig. 4. KCC2 content in the spinal cord of experimental animals. C – control; CL – control + CLP290 administration for 7 days; HS – suspension for 7 days; HSL – suspension for 7 days with daily administration of CLP290. Data are presented as mean ± σ. * – difference from control (p < 0.05).

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6. Fig. 5. Cross-sectional area of ​​slow (a) and fast (b) muscle fibers in rat soleus m. C – control; CL – suspension + CLP290 administration for 7 days; HS – suspension for 7 days; HSL – suspension + CLP290 administration for 7 days. * – difference from control (p < 0.05).

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