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Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity

INTRODUCTION: Spinal cord injury (SCI) often causes muscle spasticity, which can be inhibited by using calcium channel blocker. Botulinum toxin type A (BoT-A) shows therapeutic efficacy on spasticity and may exert inhibitory effects on the calcium channel. METHODS: A rat model with muscle spasticity...

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Autores principales: Ma, Kening, Zhu, Dan, Zhang, Chunguo, Lv, Lijie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395704/
https://www.ncbi.nlm.nih.gov/pubmed/32801642
http://dx.doi.org/10.2147/DDDT.S256814
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author Ma, Kening
Zhu, Dan
Zhang, Chunguo
Lv, Lijie
author_facet Ma, Kening
Zhu, Dan
Zhang, Chunguo
Lv, Lijie
author_sort Ma, Kening
collection PubMed
description INTRODUCTION: Spinal cord injury (SCI) often causes muscle spasticity, which can be inhibited by using calcium channel blocker. Botulinum toxin type A (BoT-A) shows therapeutic efficacy on spasticity and may exert inhibitory effects on the calcium channel. METHODS: A rat model with muscle spasticity was established after SCI via contusion and compression. Different concentrations (0, 1, 3 and 6 U/kg) of BoT-A Botox were injected in the extensor digitorum longus (EDL) muscles of the right hindlimb in the muscle spasticity model. The changes of muscle spasticity and calcium level in EDL muscles were measured after the establishment of SCI-induced spasticity. Ca(v)3.2 calcium channel subunit and its mutant (M1560V) were analyzed using Western blot before (input) or after immunoprecipitation with anti-FLAG antibody, and their currents were measured in motoneurons by using whole-cell voltage clamp recordings. RESULTS: SCI induced muscle spasticity, whereas calcium level in EDL muscles and expression of Ca(v)3.2 was increased in the SCI model when compared with the sham group (p < 0.05). BoT-A Botox treatment significantly reduced muscle spasticity and calcium level in EDL muscles and Ca(v)3.2 expression in a dose-dependent way (p < 0.05). The ratio of biotinylated to total Ca(v)3.2 was reduced in the mutant (M1560V) of Ca(v)3.2 and lower than that in the wild Ca(v)3.2. BoT-A Botox intervention also reduced the current values of calcium channel and the ratio in a dose-dependent way (p < 0.05). DISCUSSION: BoT-A Botox possibly attenuates SCI-induced muscle spasticity by affecting the expression of Ca(v)3.2 calcium channel subunit in the rat models. There may be multiple mechanisms for the function of BoT-A Botox. Further work is needed to be done to address these issues.
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spelling pubmed-73957042020-08-13 Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity Ma, Kening Zhu, Dan Zhang, Chunguo Lv, Lijie Drug Des Devel Ther Original Research INTRODUCTION: Spinal cord injury (SCI) often causes muscle spasticity, which can be inhibited by using calcium channel blocker. Botulinum toxin type A (BoT-A) shows therapeutic efficacy on spasticity and may exert inhibitory effects on the calcium channel. METHODS: A rat model with muscle spasticity was established after SCI via contusion and compression. Different concentrations (0, 1, 3 and 6 U/kg) of BoT-A Botox were injected in the extensor digitorum longus (EDL) muscles of the right hindlimb in the muscle spasticity model. The changes of muscle spasticity and calcium level in EDL muscles were measured after the establishment of SCI-induced spasticity. Ca(v)3.2 calcium channel subunit and its mutant (M1560V) were analyzed using Western blot before (input) or after immunoprecipitation with anti-FLAG antibody, and their currents were measured in motoneurons by using whole-cell voltage clamp recordings. RESULTS: SCI induced muscle spasticity, whereas calcium level in EDL muscles and expression of Ca(v)3.2 was increased in the SCI model when compared with the sham group (p < 0.05). BoT-A Botox treatment significantly reduced muscle spasticity and calcium level in EDL muscles and Ca(v)3.2 expression in a dose-dependent way (p < 0.05). The ratio of biotinylated to total Ca(v)3.2 was reduced in the mutant (M1560V) of Ca(v)3.2 and lower than that in the wild Ca(v)3.2. BoT-A Botox intervention also reduced the current values of calcium channel and the ratio in a dose-dependent way (p < 0.05). DISCUSSION: BoT-A Botox possibly attenuates SCI-induced muscle spasticity by affecting the expression of Ca(v)3.2 calcium channel subunit in the rat models. There may be multiple mechanisms for the function of BoT-A Botox. Further work is needed to be done to address these issues. Dove 2020-07-28 /pmc/articles/PMC7395704/ /pubmed/32801642 http://dx.doi.org/10.2147/DDDT.S256814 Text en © 2020 Ma et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Ma, Kening
Zhu, Dan
Zhang, Chunguo
Lv, Lijie
Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title_full Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title_fullStr Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title_full_unstemmed Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title_short Botulinum Toxin Type A Possibly Affects Ca(v)3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity
title_sort botulinum toxin type a possibly affects ca(v)3.2 calcium channel subunit in rats with spinal cord injury-induced muscle spasticity
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395704/
https://www.ncbi.nlm.nih.gov/pubmed/32801642
http://dx.doi.org/10.2147/DDDT.S256814
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