Abstract
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+)/chloride (Cl−) 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.
Highlights
A number of authors have repeatedly shown that following 3–4 days of mechanical unloading, rat soleus muscle resumes its electromyographic (EMG) activity [1,2,3]
We aimed to investigate the effect of prochlorperazine on the emergence of delayed onset electrical activity of the rat soleus muscle under hindlimb unloading
Graph shows that 7-day hindlimb suspension/unloading led to a significant decrease in both total content and phosphorylation of KCC2 in spinal motoneurons
Summary
A number of authors have repeatedly shown that following 3–4 days of mechanical unloading (hindlimb suspension, HS), rat soleus muscle resumes its electromyographic (EMG) activity [1,2,3] This EMG activity is apparently not associated with reflex responses to some stimuli. The elimination of the propagation of action potential via denervation of the soleus muscle during 14-day HS does not result in greater muscle atrophy [4] In this regard, the phenomenon of increased excitability of motoneurons due to changes in potassium (K+)/chloride (Cl−) co-transporter 2 (KCC2) is of great interest [5,6]. It is important to note that equilibrium potential for Cl− is dependent on the activity of Na(+)/K(+)/Cl(−) co-transporter isoform 1 (NKCC1), a membrane protein that mediates active transport of sodium, potassium, and chloride into cells [8]
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