Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation-transcription coupling

Leonid V. Kapilevich, Tatyana A. Kironenko, Anna N. Zaharova, Yuri V. Kotelevtsev, Nickolai O. Dulin, Sergei N. Orlov

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin-6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies.

Original languageEnglish
Pages (from-to)328-336
Number of pages9
JournalGenes and Diseases
Volume2
Issue number4
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Fingerprint

Transcription
Muscle
Skeletal Muscle
Voltage-Gated Potassium Channels
Hypoxia-Inducible Factor 1
Monovalent Cations
AMP-Activated Protein Kinases
Cyclooxygenase 2
Chelating Agents
Interleukin-2
Interleukin-6
Genes
Chemical activation
Electric potential
Research

Keywords

  • Myokines
  • Secretion
  • Skeletal muscle
  • Transcription
  • Translation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics(clinical)
  • Cell Biology

Cite this

Skeletal muscle as an endocrine organ : Role of [Na+]i/[K+]i-mediated excitation-transcription coupling. / Kapilevich, Leonid V.; Kironenko, Tatyana A.; Zaharova, Anna N.; Kotelevtsev, Yuri V.; Dulin, Nickolai O.; Orlov, Sergei N.

In: Genes and Diseases, Vol. 2, No. 4, 01.12.2015, p. 328-336.

Research output: Contribution to journalReview article

Kapilevich, Leonid V. ; Kironenko, Tatyana A. ; Zaharova, Anna N. ; Kotelevtsev, Yuri V. ; Dulin, Nickolai O. ; Orlov, Sergei N. / Skeletal muscle as an endocrine organ : Role of [Na+]i/[K+]i-mediated excitation-transcription coupling. In: Genes and Diseases. 2015 ; Vol. 2, No. 4. pp. 328-336.
@article{a230a37763d74d57933794abe762e2ca,
title = "Skeletal muscle as an endocrine organ: Role of [Na+]i/[K+]i-mediated excitation-transcription coupling",
abstract = "During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin-6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies.",
keywords = "Myokines, Secretion, Skeletal muscle, Transcription, Translation",
author = "Kapilevich, {Leonid V.} and Kironenko, {Tatyana A.} and Zaharova, {Anna N.} and Kotelevtsev, {Yuri V.} and Dulin, {Nickolai O.} and Orlov, {Sergei N.}",
year = "2015",
month = "12",
day = "1",
doi = "10.1016/j.gendis.2015.10.001",
language = "English",
volume = "2",
pages = "328--336",
journal = "Genes and Diseases",
issn = "2352-3042",
publisher = "Elsevier BV",
number = "4",

}

TY - JOUR

T1 - Skeletal muscle as an endocrine organ

T2 - Role of [Na+]i/[K+]i-mediated excitation-transcription coupling

AU - Kapilevich, Leonid V.

AU - Kironenko, Tatyana A.

AU - Zaharova, Anna N.

AU - Kotelevtsev, Yuri V.

AU - Dulin, Nickolai O.

AU - Orlov, Sergei N.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin-6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies.

AB - During the last two decades numerous research teams demonstrated that skeletal muscles function as an exercise-dependent endocrine organ secreting dozens of myokines. Variety of physiological and pathophysiological implications of skeletal muscle myokines secretion has been described; however, upstream signals and sensing mechanisms underlying this phenomenon remain poorly understood. It is well documented that in skeletal muscles intensive exercise triggers dissipation of transmembrane gradient of monovalent cations caused by permanent activation of voltage-gated Na+ and K+ channels. Recently, we demonstrated that sustained elevation of the [Na+]i/[K+]i ratio triggers expression of dozens ubiquitous genes including several canonical myokines, such as interleukin-6 and cyclooxygenase 2, in the presence of intra- and extracellular Ca2+ chelators. These data allowed us to suggest a novel [Na+]i/[K+]i-sensitive, Ca2+i-independent mechanism of excitation-transcription coupling which triggers myokine production. This pathway exists in parallel with canonical signaling mediated by Ca2+i, AMP-activated protein kinase and hypoxia-inducible factor 1α (HIF-1α). In our mini-review we briefly summarize data supporting this hypothesis as well as unresolved issues aiming to forthcoming studies.

KW - Myokines

KW - Secretion

KW - Skeletal muscle

KW - Transcription

KW - Translation

UR - http://www.scopus.com/inward/record.url?scp=84978091736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84978091736&partnerID=8YFLogxK

U2 - 10.1016/j.gendis.2015.10.001

DO - 10.1016/j.gendis.2015.10.001

M3 - Review article

AN - SCOPUS:84978091736

VL - 2

SP - 328

EP - 336

JO - Genes and Diseases

JF - Genes and Diseases

SN - 2352-3042

IS - 4

ER -