Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study

A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3–4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of moto...

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Autores principales:	Vitaliy E. Kalashnikov, Sergey A. Tyganov, Olga V. Turtikova, Ekaterina P. Kalashnikova, Margarita V. Glazova, Timur M. Mirzoev, Boris S. Shenkman
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	soleus muscle EMG activity hindlimb suspension KCC2 NKCC1 prochlorperazine Science Q
Acceso en línea:	https://doaj.org/article/572c69f738104c5eb6db5538597c46a5
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spelling	oai:doaj.org-article:572c69f738104c5eb6db5538597c46a52021-11-25T18:10:48ZProchlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study10.3390/life111111612075-1729https://doaj.org/article/572c69f738104c5eb6db5538597c46a52021-10-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1161https://doaj.org/toc/2075-1729A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3–4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of motoneurons and muscle spasticity after spinal cord injury are associated with KCC2 downregulation, we hypothesized that a decrease in potassium (K<sup>+</sup>)/chloride (Cl<sup>−</sup>) co-transporter 2 (KCC2) in motoneurons would be responsible for an increase in soleus muscle EMG activity during HS. We aimed to investigate the effect of prochlorperazine (KCC2 activator) on the electrical activity of rat soleus muscle under HS. Wistar rats were divided into the following groups: (1) vivarium control (C), (2) 7-day HS group (7HS) and (3) 7-day HS group plus intraperitoneal injections of prochlorperazine (10 mg/kg, daily) (7HS + P). Expression of proteins in the motoneurons of the lumbar spinal cord was determined by Western blotting. An electromyogram of the rat soleus muscle was recorded using intramuscular electrodes. KCC2 content after 7-day HS significantly decreased by 34% relative to the control group. HS-induced decrease in KCC2 protein content was prevented by prochlorperazine administration. HS also induced a significant 80% decrease in KCC2 Ser940 phosphorylation; however prochlorperazine did not affect KCC2 phosphorylation. The treatment of the rats with prochlorperazine prevented a HS-induced increase in Na(+)/K(+)/(Cl−) co-transporter 1 (KCC2 antagonist) protein content. In parallel with the restoration of KCC2 content, prochlorperazine administration during HS partially prevented an increase in the soleus muscle tonic EMG activity. Thus, prochlorperazine administration during 7-day HS prevents a decrease in KCC2 protein expression in motoneurons and significantly reduces the level of HS-induced soleus muscle electrical activity.Vitaliy E. KalashnikovSergey A. TyganovOlga V. TurtikovaEkaterina P. KalashnikovaMargarita V. GlazovaTimur M. MirzoevBoris S. ShenkmanMDPI AGarticlesoleus muscleEMG activityhindlimb suspensionKCC2NKCC1prochlorperazineScienceQENLife, Vol 11, Iss 1161, p 1161 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	soleus muscle EMG activity hindlimb suspension KCC2 NKCC1 prochlorperazine Science Q
spellingShingle	soleus muscle EMG activity hindlimb suspension KCC2 NKCC1 prochlorperazine Science Q Vitaliy E. Kalashnikov Sergey A. Tyganov Olga V. Turtikova Ekaterina P. Kalashnikova Margarita V. Glazova Timur M. Mirzoev Boris S. Shenkman Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
description	A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3–4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of motoneurons and muscle spasticity after spinal cord injury are associated with KCC2 downregulation, we hypothesized that a decrease in potassium (K<sup>+</sup>)/chloride (Cl<sup>−</sup>) co-transporter 2 (KCC2) in motoneurons would be responsible for an increase in soleus muscle EMG activity during HS. We aimed to investigate the effect of prochlorperazine (KCC2 activator) on the electrical activity of rat soleus muscle under HS. Wistar rats were divided into the following groups: (1) vivarium control (C), (2) 7-day HS group (7HS) and (3) 7-day HS group plus intraperitoneal injections of prochlorperazine (10 mg/kg, daily) (7HS + P). Expression of proteins in the motoneurons of the lumbar spinal cord was determined by Western blotting. An electromyogram of the rat soleus muscle was recorded using intramuscular electrodes. KCC2 content after 7-day HS significantly decreased by 34% relative to the control group. HS-induced decrease in KCC2 protein content was prevented by prochlorperazine administration. HS also induced a significant 80% decrease in KCC2 Ser940 phosphorylation; however prochlorperazine did not affect KCC2 phosphorylation. The treatment of the rats with prochlorperazine prevented a HS-induced increase in Na(+)/K(+)/(Cl−) co-transporter 1 (KCC2 antagonist) protein content. In parallel with the restoration of KCC2 content, prochlorperazine administration during HS partially prevented an increase in the soleus muscle tonic EMG activity. Thus, prochlorperazine administration during 7-day HS prevents a decrease in KCC2 protein expression in motoneurons and significantly reduces the level of HS-induced soleus muscle electrical activity.
format	article
author	Vitaliy E. Kalashnikov Sergey A. Tyganov Olga V. Turtikova Ekaterina P. Kalashnikova Margarita V. Glazova Timur M. Mirzoev Boris S. Shenkman
author_facet	Vitaliy E. Kalashnikov Sergey A. Tyganov Olga V. Turtikova Ekaterina P. Kalashnikova Margarita V. Glazova Timur M. Mirzoev Boris S. Shenkman
author_sort	Vitaliy E. Kalashnikov
title	Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
title_short	Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
title_full	Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
title_fullStr	Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
title_full_unstemmed	Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study
title_sort	prochlorperazine withdraws the delayed onset tonic activity of unloaded rat soleus muscle: a pilot study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/572c69f738104c5eb6db5538597c46a5
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Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study

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