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

J Membr Biol. 2012 Aug;245(8):423-36. doi: 10.1007/s00232-012-9485-8. Epub 2012 Aug 1.


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 Ca(2+) 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.

Publication types

  • Review

MeSH terms

  • Animals
  • Connexins / metabolism*
  • Humans
  • Ion Channel Gating*
  • Models, Biological*
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Reference Values


  • Connexins
  • Nerve Tissue Proteins
  • PANX1 protein, human