Research output: Contribution to journal › Article › peer-review
Chronic ouabain prevents na,k-atpase dysfunction and targets ampk and il-6 in disused rat soleus muscle. / Kravtsova, Violetta V.; Paramonova, Inna I.; Vilchinskaya, Natalia A.; Tishkova, Maria V.; Matchkov, Vladimir V.; Shenkman, Boris S.; Krivoi, Igor I.
In: International Journal of Molecular Sciences, Vol. 22, No. 8, 3920, 10.04.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Chronic ouabain prevents na,k-atpase dysfunction and targets ampk and il-6 in disused rat soleus muscle
AU - Kravtsova, Violetta V.
AU - Paramonova, Inna I.
AU - Vilchinskaya, Natalia A.
AU - Tishkova, Maria V.
AU - Matchkov, Vladimir V.
AU - Shenkman, Boris S.
AU - Krivoi, Igor I.
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/10
Y1 - 2021/4/10
N2 - Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is char-acteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its dis-use-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with oua-bain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were stud-ied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemis-try were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depo-larization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate ac-etyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of inter-leikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.
AB - Sustained sarcolemma depolarization due to loss of the Na,K-ATPase function is char-acteristic for skeletal muscle motor dysfunction. Ouabain, a specific ligand of the Na,K-ATPase, has a circulating endogenous analogue. We hypothesized that the Na,K-ATPase targeted by the elevated level of circulating ouabain modulates skeletal muscle electrogenesis and prevents its dis-use-induced disturbances. Isolated soleus muscles from rats intraperitoneally injected with oua-bain alone or subsequently exposed to muscle disuse by 6-h hindlimb suspension (HS) were stud-ied. Conventional electrophysiology, Western blotting, and confocal microscopy with cytochemis-try were used. Acutely applied 10 nM ouabain hyperpolarized the membrane. However, a single injection of ouabain (1 µg/kg) prior HS was unable to prevent the HS-induced membrane depo-larization. Chronic administration of ouabain for four days did not change the α1 and α2 Na,K-ATPase protein content, however it partially prevented the HS-induced loss of the Na,K-ATPase electrogenic activity and sarcolemma depolarization. These changes were associated with increased phosphorylation levels of AMP-activated protein kinase (AMPK), its substrate ac-etyl-CoA carboxylase and p70 protein, accompanied with increased mRNA expression of inter-leikin-6 (IL-6) and IL-6 receptor. Considering the role of AMPK in regulation of the Na,K-ATPase, we suggest an IL-6/AMPK contribution to prevent the effects of chronic ouabain under skeletal muscle disuse.
KW - AMP-activated protein kinase
KW - Hindlimb suspension
KW - Na,K-ATPase isozymes
KW - Ouabain
KW - Resting membrane potential
KW - Skeletal muscle
KW - ouabain
KW - Na
KW - K-ATPase isozymes
KW - resting membrane potential
KW - hindlimb suspension
KW - skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=85103834771&partnerID=8YFLogxK
U2 - 10.3390/ijms22083920
DO - 10.3390/ijms22083920
M3 - Article
C2 - 33920198
AN - SCOPUS:85103834771
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 8
M1 - 3920
ER -
ID: 77796425