Changes in contractile characteristics of rat skeletal muscles associated with P2-receptor activation after spinal cord transection

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Introduction. Traumatic spinal cord and peripheral-nerve injury is associated with release of proinflammatory cytokines and chemokines, which may stimulate neuronal activity. Adenosine triphosphoric acid (ATP) is an important pain mediator involved in the acute and chronic neuropathic pain development. Its excessive release from primary injured tissue leads to activation of P2-receptors, which may further start secondary injury mechanisms. Although the effects of ATP on the peripheral nervous system are relatively well studied, the pathophysiological role of purinergic signaling after spinalization remains unclear.

The study was aimed at assessing the post-spinalization effects of P2-receptors on the contractile characteristics of rat skeleton muscles.

Materials and methods. The objects of the study were the soleus muscle, the extensor digitorum longus (EDL) muscle, and diaphragm in intact rats and spinalized rats. Seven days after laminectomy followed by spinal cord transection, animals were anesthetized, exsanguinated, and their muscles with nerve stumps were isolated. Contractile response parameters were recorded using mechanomyography (MMG). To study effects of ATP on ligand binding, ATP was added to a bath and mechanical responses in the rat muscles were assessed 7 min after. After washing with Krebs–Henseleit solution, the preparations were incubated with suramin solution for 20 min with subsequent ATP application. Then the mechanical responses in the muscles were again recorded. Statistical significance was assessed using Student's t-test for independent (unpaired) and paired samples.

Results. We found a significant (p < 0.05) decrease in the modulating activity of ATP, as the main endogenous signaling agent, in the cholinergic synapse of the soleus muscle from 32.4 to 5.8% and from 13.7 to 5.6% for the EDL muscle after the spinalization (spinal cord injury at the Th6–Th7 level) compared with intact animals. No such dramatic changes were observed in the diaphragm.

Conclusions. Abnormal ATP-mediated modulation of neuromuscular transmission demonstrated in this study supports the involvement of purinergic signaling in the neurotrophic control and functioning of various motor units.

About the authors

Adel E. Khairullin

Kazan State Medical University; Kazan (Volga Region) Federal University

Author for correspondence.
Email: khajrulli@ya.ru
ORCID iD: 0000-0001-6155-622X

Cand. Sci. (Biol.), Assistant Professor, Department of biochemistry and clinical laboratory diagnostics, Kazan State Medical University; senior researcher, Research laboratory «Mechanobiology», Institute of Fundamental Medicine and Biology, Kazan Federal University

Russian Federation, Kazan; Kazan

Dina V. Efimova

Kazan State Medical University

Email: khajrulli@ya.ru
ORCID iD: 0009-0000-3966-0813

postgraduate student, Department of biochemistry and clinical laboratory diagnostics, Kazan State Medical University

Russian Federation, Kazan

Marat A. Mukhamedyarov

Kazan State Medical University

Email: marat.muhamedyarov@kazangmu.ru
ORCID iD: 0000-0002-0397-9002

D. Sci. (Med.), Professor, Head, Department of normal physiology, Kazan State Medical University

Russian Federation, Kazan

Maxim E. Baltin

Kazan (Volga Region) Federal University

Email: khajrulli@ya.ru
ORCID iD: 0000-0001-5005-1699

researcher, Research laboratory «Mechanobiology», Institute of Fundamental Medicine and Biology, Kazan Federal University

Russian Federation, Kazan

Tatiana V. Baltina

Kazan (Volga Region) Federal University

Email: khajrulli@ya.ru
ORCID iD: 0000-0003-3798-7665

Cand. Sci. (Biol.), Associate Professor, Head, Research laboratory «Mechanobiology», Institute of Fundamental Medicine and Biology, Kazan Federal University

Russian Federation, Kazan

Sergey N. Grishin

Kazan State Medical University

Email: sgrishin@inbox.ru
ORCID iD: 0000-0002-2851-579X

D. Sci. (Biol.), Professor, Department of medical and bio- logical physics with computer science and medical equipment, Kazan State Medical University

Russian Federation, Kazan

Airat U. Ziganshin

Kazan State Medical University

Email: airat.ziganshin@kazangmu.ru
ORCID iD: 0000-0002-9087-7927

D. Sci. (Med.), Professor, Head, Department of pharmacology, Kazan State Medical University

Russian Federation, Kazan

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2. Fig. 1. Schematic diagram of spinalization at Th6–Th7.

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3. Fig. 2. Traces of single contractile responses of the isolated rat m. soleus, m. EDL and m. diaphragma evoked by electrical stimulation in controls and in spinalized rats (selected representative traces are presented).

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Copyright (c) 2024 Khairullin A.E., Efimova D.V., Mukhamedyarov M.A., Baltin M.E., Baltina T.V., Grishin S.N., Ziganshin A.U.

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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