AMPK and glucose deprivation exert an isoform-specific effect on the expression of Na$^+$,K$^+$-ATPase subunits in cultured myotubes

Vidović, Anja (author), Dolinar, Klemen (author), Chibalin, Alexander V. (author), Pirkmajer, Sergej (author)

In skeletal muscle, Na$^+$,K$^+$-ATPase (NKA), a heterodimeric (α/β) P-type ATPase, has an essential role in maintenance of Na$^+$ and K$^+$ homeostasis, excitability, and contractility. AMP-activated protein kinase (AMPK), an energy sensor, increases the membrane abundance and activity of NKA in L6 myotubes, but its potential role in regulation of NKA content in skeletal muscle, which determines maximum capacity for Na$^+$ and K$^+$ transport, has not been clearly delineated. We examined whether energy stress and/or AMPK affect expression of NKA subunits in rat L6 and primary human myotubes. Energy stress, induced by glucose deprivation, increased protein content of NKAα1 and NKAα2 in L6 myotubes, while decreasing the content of NKAα1 in human myotubes. Pharmacological AMPK activators (AICAR, A-769662, and diflunisal) modulated expression of NKA subunits, but their effects only partially mimicked those that occurred in response to glucose deprivation, indicating that AMPK does not mediate all effects of energy stress on NKA expression. Gene silencing of AMPKα1/α2 increased protein levels of NKAα1 in L6 myotubes and NKAα1 mRNA levels in human myotubes, while decreasing NKAα2 protein levels in L6 myotubes. Collectively, our results suggest a role for energy stress and AMPK in modulation of NKA expression in skeletal muscle. However, their modulatory effects were not conserved between L6 myotubes and primary human myotubes, which suggests that coupling between energy stress, AMPK, and regulation of NKA expression in vitro depends on skeletal muscle cell model.

• Language: English
• Keywords: AMPK, energy stress, glucose, myotubes, Na$^+$, K$^+$-ATPase, skeletal muscle
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: Str. 139-154
• Numbering: Vol. 45, iss. 3
• PID: 20.500.12556/RUL-160108
• UDC: 616-092
• ISSN on article: 1573-2657
• DOI: 10.1007/s10974-024-09673-9
• COBISS.SI-ID: 194665731
• Publication date in RUL: 21.08.2024

Record is a part of a journal

• Title: Journal of muscle research and cell motility
• Shortened title: J. muscle res. cell motil.
• Publisher: Springer Nature
• ISSN: 1573-2657
• COBISS.SI-ID: 513197337

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: energijski stres, glukoza, miocevke, skeletna mišica