Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy

Luis A. Cea, Manuel A. Riquelme, Bruno A. Cisterna, Carlos Puebla, José L. Vega, Maximiliano Rovegno, Juan C. Sáez

Resultado de la investigación: Review article

26 Citas (Scopus)

Resumen

Precursor cells of skeletal muscles express connexins 39, 43 and 45 and pannexin1. In these cells, most connexins form two types of membrane channels, gap junction channels and hemichannels, whereas pannexin1 forms only hemichannels. All these channels are low-resistance pathways permeable to ions and small molecules that coordinate developmental events. During late stages of skeletal muscle differentiation, myofibers become innervated and stop expressing connexins but still express pannexin1 hemichannels that are potential pathways for the ATP release required for potentiation of the contraction response. Adult injured muscles undergo regeneration, and connexins are reexpressed and form membrane channels. In vivo, connexin reexpression occurs in undifferentiated cells that form new myofibers, favoring the healing process of injured muscle. However, differentiated myofibers maintained in culture for 48 h or treated with proinflammatory cytokines for less than 3 h also reexpress connexins and only form functional hemichannels at the cell surface. We propose that opening of these hemichannels contributes to drastic changes in electrochemical gradients, including reduction of membrane potential, increases in intracellular free Ca2+ concentration and release of diverse metabolites (e.g., NAD + and ATP) to the extracellular milieu, contributing to multiple metabolic and physiologic alterations that characterize muscles undergoing atrophy in several acquired and genetic human diseases. Consequently, inhibition of connexin hemichannels expressed by injured or denervated skeletal muscles might reduce or prevent deleterious changes triggered by conditions that promote muscle atrophy.

Idioma originalEnglish
Páginas (desde-hasta)423-436
Número de páginas14
PublicaciónJournal of Membrane Biology
Volumen245
N.º8
DOI
EstadoPublished - ago 2012

Huella dactilar

Connexins
Muscular Atrophy
Skeletal Muscle
Ion Channels
Adenosine Triphosphate
Muscles
Connexin 43
Inborn Genetic Diseases
Gap Junctions
NAD
Membrane Potentials
Regeneration
Ions
Cytokines

ASJC Scopus subject areas

  • Biophysics
  • Physiology
  • Cell Biology

Citar esto

Cea, L. A., Riquelme, M. A., Cisterna, B. A., Puebla, C., Vega, J. L., Rovegno, M., & Sáez, J. C. (2012). Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy. Journal of Membrane Biology, 245(8), 423-436. https://doi.org/10.1007/s00232-012-9485-8
Cea, Luis A. ; Riquelme, Manuel A. ; Cisterna, Bruno A. ; Puebla, Carlos ; Vega, José L. ; Rovegno, Maximiliano ; Sáez, Juan C. / Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy. En: Journal of Membrane Biology. 2012 ; Vol. 245, N.º 8. pp. 423-436.
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abstract = "Precursor cells of skeletal muscles express connexins 39, 43 and 45 and pannexin1. In these cells, most connexins form two types of membrane channels, gap junction channels and hemichannels, whereas pannexin1 forms only hemichannels. All these channels are low-resistance pathways permeable to ions and small molecules that coordinate developmental events. During late stages of skeletal muscle differentiation, myofibers become innervated and stop expressing connexins but still express pannexin1 hemichannels that are potential pathways for the ATP release required for potentiation of the contraction response. Adult injured muscles undergo regeneration, and connexins are reexpressed and form membrane channels. In vivo, connexin reexpression occurs in undifferentiated cells that form new myofibers, favoring the healing process of injured muscle. However, differentiated myofibers maintained in culture for 48 h or treated with proinflammatory cytokines for less than 3 h also reexpress connexins and only form functional hemichannels at the cell surface. We propose that opening of these hemichannels contributes to drastic changes in electrochemical gradients, including reduction of membrane potential, increases in intracellular free Ca2+ concentration and release of diverse metabolites (e.g., NAD + and ATP) to the extracellular milieu, contributing to multiple metabolic and physiologic alterations that characterize muscles undergoing atrophy in several acquired and genetic human diseases. Consequently, inhibition of connexin hemichannels expressed by injured or denervated skeletal muscles might reduce or prevent deleterious changes triggered by conditions that promote muscle atrophy.",
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Cea, LA, Riquelme, MA, Cisterna, BA, Puebla, C, Vega, JL, Rovegno, M & Sáez, JC 2012, 'Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy', Journal of Membrane Biology, vol. 245, n.º 8, pp. 423-436. https://doi.org/10.1007/s00232-012-9485-8

Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy. / Cea, Luis A.; Riquelme, Manuel A.; Cisterna, Bruno A.; Puebla, Carlos; Vega, José L.; Rovegno, Maximiliano; Sáez, Juan C.

En: Journal of Membrane Biology, Vol. 245, N.º 8, 08.2012, p. 423-436.

Resultado de la investigación: Review article

TY - JOUR

T1 - Connexin-and pannexin-based channels in normal skeletal muscles and their possible role in muscle atrophy

AU - Cea, Luis A.

AU - Riquelme, Manuel A.

AU - Cisterna, Bruno A.

AU - Puebla, Carlos

AU - Vega, José L.

AU - Rovegno, Maximiliano

AU - Sáez, Juan C.

PY - 2012/8

Y1 - 2012/8

N2 - Precursor cells of skeletal muscles express connexins 39, 43 and 45 and pannexin1. In these cells, most connexins form two types of membrane channels, gap junction channels and hemichannels, whereas pannexin1 forms only hemichannels. All these channels are low-resistance pathways permeable to ions and small molecules that coordinate developmental events. During late stages of skeletal muscle differentiation, myofibers become innervated and stop expressing connexins but still express pannexin1 hemichannels that are potential pathways for the ATP release required for potentiation of the contraction response. Adult injured muscles undergo regeneration, and connexins are reexpressed and form membrane channels. In vivo, connexin reexpression occurs in undifferentiated cells that form new myofibers, favoring the healing process of injured muscle. However, differentiated myofibers maintained in culture for 48 h or treated with proinflammatory cytokines for less than 3 h also reexpress connexins and only form functional hemichannels at the cell surface. We propose that opening of these hemichannels contributes to drastic changes in electrochemical gradients, including reduction of membrane potential, increases in intracellular free Ca2+ concentration and release of diverse metabolites (e.g., NAD + and ATP) to the extracellular milieu, contributing to multiple metabolic and physiologic alterations that characterize muscles undergoing atrophy in several acquired and genetic human diseases. Consequently, inhibition of connexin hemichannels expressed by injured or denervated skeletal muscles might reduce or prevent deleterious changes triggered by conditions that promote muscle atrophy.

AB - Precursor cells of skeletal muscles express connexins 39, 43 and 45 and pannexin1. In these cells, most connexins form two types of membrane channels, gap junction channels and hemichannels, whereas pannexin1 forms only hemichannels. All these channels are low-resistance pathways permeable to ions and small molecules that coordinate developmental events. During late stages of skeletal muscle differentiation, myofibers become innervated and stop expressing connexins but still express pannexin1 hemichannels that are potential pathways for the ATP release required for potentiation of the contraction response. Adult injured muscles undergo regeneration, and connexins are reexpressed and form membrane channels. In vivo, connexin reexpression occurs in undifferentiated cells that form new myofibers, favoring the healing process of injured muscle. However, differentiated myofibers maintained in culture for 48 h or treated with proinflammatory cytokines for less than 3 h also reexpress connexins and only form functional hemichannels at the cell surface. We propose that opening of these hemichannels contributes to drastic changes in electrochemical gradients, including reduction of membrane potential, increases in intracellular free Ca2+ concentration and release of diverse metabolites (e.g., NAD + and ATP) to the extracellular milieu, contributing to multiple metabolic and physiologic alterations that characterize muscles undergoing atrophy in several acquired and genetic human diseases. Consequently, inhibition of connexin hemichannels expressed by injured or denervated skeletal muscles might reduce or prevent deleterious changes triggered by conditions that promote muscle atrophy.

KW - Cell-cell channel

KW - Gap junction

KW - Pharmacology of muscle diseases

KW - Physiology of calcium channels in muscle

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M3 - Review article

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