Bulletin of Experimental Biology and Medicine

, Volume 166, Issue 5, pp 593–597 | Cite as

Abnormal Membrane Localization of α2 Isoform of Na,K-ATPase in m. soleus of Dysferlin-Deficient Mice

  • V. V. Kravtsova
  • E. V. Bouzinova
  • V. V. Machkov
  • N. A. Timonina
  • G. F. Zakyrjanova
  • A. L. Zefirov
  • I. I. KrivoiEmail author

Dysferlin protein plays a key role in the multimolecular complex responsible for the maintenance of sarcolemma integrity and skeletal muscle cell functioning. We studied the membrane distribution of nicotinic acetylcholine receptors and α2 isoform of Na,K-ATPase in motor endplates of m. soleus in dysferlin-deficient Bla/J mice (a dysferlinopathy model). Endplates of Bla/J mice were characterized by increased area (without changes in fragmentation degree) and reduced density of the membrane distribution of nicotinic acetylcholine receptors in comparison with the corresponding parameters in control С57Bl/6 mice. The density of the membrane distribution of α2 isoform of Na,K-ATPase was also reduced, but the level of the corresponding mRNA remained unchanged. It can be hypothesized that abnormal membrane localization of α2 isoform of Na,K-ATPase results from adaptive skeletal muscle remodeling under conditions of chronic motor dysfunction.

Key Words

skeletal muscle dysferlin dysferlinopathy Na,K-ATPase isoforms nicotinic acetylcholine receptors 


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  1. 1.
    Cárdenas AM, González-Jamett AM, Cea LA, Bevilacqua JA, Caviedes P. Dysferlin function in skeletal muscle: Possible pathological mechanisms and therapeutical targets in dysferlinopathies. Exp. Neurol. 2016;283(Pt A):246-254.CrossRefPubMedGoogle Scholar
  2. 2.
    Chibalin AV, Benziane B, Zakyrjanova GF, Kravtsova VV, Krivoi II. Early endplate remodeling and skeletal muscle signaling events following rat hindlimb suspension. J. Cell. Physiol. 2018;233(10):6329-6336.CrossRefPubMedGoogle Scholar
  3. 3.
    Clausen T. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: functional significance. J. Gen. Physiol. 2013;142(4):327-345.CrossRefPubMedGoogle Scholar
  4. 4.
    DiFranco M, Hakimjavadi H, Lingrel JB, Heiny JA. Na,K-ATPase α2 activity in mammalian skeletal muscle T-tubules is acutely stimulated by extracellular K+. J. Gen. Physiol. 2015;146(4):281-294.CrossRefPubMedGoogle Scholar
  5. 5.
    He S, Shelly DA, Moseley AE, James PF, James JH, Paul RJ, Lingrel JB. The alpha(1)- and alpha(2)-isoforms of Na-K-ATPase play different roles in skeletal muscle contractility. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2001;281(3):R917-R925.CrossRefPubMedGoogle Scholar
  6. 6.
    Heiny JA, Kravtsova VV, Mandel F, Radzyukevich TL, Benziane B, Prokofiev AV, Pedersen SE, Chibalin AV, Krivoi II. The nicotinic acetylcholine receptor and the Na,K-ATPase alpha2 isoform interact to regulate membrane electrogenesis in skeletal muscle. J. Biol. Chem. 2010;285(37):28,614-28,626.CrossRefGoogle Scholar
  7. 7.
    Kravtsova VV, Petrov AM, Matchkov VV, Bouzinova EV, Vasiliev AN, Benziane B, Zefirov AL, Chibalin AV, Heiny JA, Krivoi II. Distinct α2 Na,K-ATPase membrane pools are differently involved in early skeletal muscle remodeling during disuse. J. Gen. Physiol. 2016;147(2):175-188.CrossRefPubMedGoogle Scholar
  8. 8.
    Kravtsova VV, Petrov AM, Vasil’ev AN, Zefirov AL, Krivoi II. Role of cholesterol in the maintenance of endplate electrogenesis in rat diaphragm. Bull. Exp. Biol. Med. 2015;158(3):298-300.CrossRefPubMedGoogle Scholar
  9. 9.
    Matchkov VV, Krivoi II. Specialized Functional Diversity and Interactions of the Na,K-ATPase. Front. Physiol. 2016;7. ID 179. doi:
  10. 10.
    McKenna MJ, Perry BD, Serpiello FR, Caldow MK, Levinger P, Cameron-Smith D, Levinger I. Unchanged [3H]ouabain binding site content but reduced Na+-K+ pump α2-protein abundance in skeletal muscle in older adults. J. Appl. Physiol. 2012;113(10):1505-1511.CrossRefPubMedGoogle Scholar
  11. 11.
    Miles MT, Cottey E, Cottey A, Stefanski C, Carlson CG. Reduced resting potentials in dystrophic (mdx) muscle fibers are secondary to NF-κB-dependent negative modulation of ouabain sensitive Na+-K+ pump activity. J. Neurosci. 2011;303(1-2):53-60.Google Scholar
  12. 12.
    Nagy N, Nonneman RJ, Llanga T, Dial CF, Riddick NV, Hampton T, Moy SS, Lehtimäki KK, Ahtoniemi T, Puoliväli J, Windish H, Albrecht D, Richard I, Hirsch ML. Hip region muscular dystrophy and emergence of motor deficits in dysferlin-deficient Bla/J mice. Physiol. Rep. 2017;5(6). pii: e13173. doi:
  13. 13.
    Perry BD, Levinger P, Morris HG, Petersen AC, Garnham AP, Levinger I, McKenna MJ. The effects of knee injury on skeletal muscle function, Na+, K+-ATPase content, and isoform abundance. Physiol. Rep. 2015;3(2. pii: e12294. doi:
  14. 14.
    Petrov AM, Kravtsova VV, Matchkov VV, Vasiliev AN, Zefirov AL, Chibalin AV, Heiny JA, Krivoi II. Membrane lipid rafts are disturbed in the response of rat skeletal muscle to shortterm disuse. Am. J. Physiol. Cell Physiol. 2017;312(5):C627-C637.CrossRefPubMedGoogle Scholar
  15. 15.
    van der Pijl EM, van Putten M, Niks EH, Verschuuren JJ, Aartsma-Rus A, Plomp JJ. Characterization of neuromuscular synapse function abnormalities in multiple Duchenne muscular dystrophy mouse models. Eur. J. Neurosci. 2016;43(12):1623-1635.CrossRefPubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • V. V. Kravtsova
    • 1
  • E. V. Bouzinova
    • 2
  • V. V. Machkov
    • 2
  • N. A. Timonina
    • 1
  • G. F. Zakyrjanova
    • 3
    • 4
  • A. L. Zefirov
    • 4
  • I. I. Krivoi
    • 1
    Email author
  1. 1.Department of General PhysiologySt. Petersburg State UniversitySt. PetersburgRussia
  2. 2.Department of BiomedicineHealth, Aarhus UniversityAarhusDenmark
  3. 3.Kazan Institute of Biochemistry and BiophysicsFederal Research Center Kazan Scientific Center of the Russian Academy of ScienceKazanRussia
  4. 4.Department of Normal PhysiologyKazan State Medical UniversityKazanRussia

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