Skip to main content

Advertisement

SpringerLink
Log in

Connexin- and Pannexin-Based Channels in Normal Skeletal Muscles and Their Possible Role in Muscle Atrophy

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adams V, Mangner N, Gasch A, Krohne C, Gielen S, Hirner S, Thierse HJ, Witt CC, Linke A, Schuler G, Labeit S (2008) Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice. J Mol Biol 384:48–59

    Article  CAS  PubMed  Google Scholar 

  • Albuquerque EX, Schuh FT, Kauffman FC (1971) Early membrane depolarization of the fast mammalian muscle after denervation. Pflügers Arch 328:36–50

    Article  CAS  PubMed  Google Scholar 

  • Alshekhlee A, Hussain Z, Sultan B, Katirji B (2008) Guillain-Barré syndrome: incidence and mortality rates in US hospitals. Neurology 70:1608–1613

    Article  PubMed  Google Scholar 

  • Ambrosi C, Gassmann O, Pranskevich JN, Boassa D, Smock A, Wang J, Dahl G, Steinem C, Sosinsky GE (2010) Pannexin1 and pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other. J Biol Chem 285:24420–24431

    Article  CAS  PubMed  Google Scholar 

  • Angel MJ, Bril V, Shannon P, Herridge MS (2007) Neuromuscular function in survivors of the acute respiratory distress syndrome. Can J Neurol Sci 34:427–432

    PubMed  Google Scholar 

  • Araya R, Eckardt D, Riquelme MA, Willecke K, Sáez JC (2003a) Presence and importance of connexin43 during myogenesis. Cell Commun Adhes 10:451–456

    CAS  PubMed  Google Scholar 

  • Araya R, Liberona JL, Cárdenas JC, Riveros N, Estrada M, Powell JA, Carrasco MA, Jaimovich E (2003b) Dihydropyridine receptors as voltage sensors for a depolarization-evoked, IP3R-mediated, slow calcium signal in skeletal muscle cells. J Gen Physiol 121:3–16

    Article  CAS  PubMed  Google Scholar 

  • Araya R, Riquelme MA, Brandan E, Sáez JC (2004) The formation of skeletal muscle myotubes requires functional membrane receptors activated by extracellular ATP. Brain Res Rev 47:174–178

    Article  CAS  PubMed  Google Scholar 

  • Araya R, Eckardt D, Maxeiner S, Kruger O, Theis M, Willecke K, Sáez JC (2005) Expression of connexins during differentiation and regeneration of skeletal muscle: functional relevance of connexin43. J Cell Sci 118:27–37

    Article  CAS  PubMed  Google Scholar 

  • Balogh S, Naus CC, Merrifield PA (1993) Expression of gap junctions in cultured rat L6 cells during myogenesis. Dev Biol 155:351–360

    Article  CAS  PubMed  Google Scholar 

  • Banachewicz W, Suplat D, Krzeminski P, Pomorski P, Baranska J (2005) P2 nucleotide receptors on C2C12 satellite cells. Purinergic Signal 1:249–257

    Article  CAS  PubMed  Google Scholar 

  • Bao L, Locovei S, Dahl G (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett 572:65–68

    Article  CAS  PubMed  Google Scholar 

  • Baranova A, Ivanov D, Petrash N, Pestova A, Skoblov M, Kelmanson I, Shagin D, Nazarenko S, Geraymovych E, Litvin O, Tiunova A, Born TL, Usman N, Staroverov D, Lukyanov S, Panchin Y (2004) The mammalian pannexin family is homologous to the invertebrate innexin gap junction proteins. Genomics 83:706–716

    Article  CAS  PubMed  Google Scholar 

  • Barrio LC, Capel J, Jarillo JA, Castro C, Revilla A (1997) Species-specific voltage-gating properties of connexin-45 junctions expressed in Xenopus oocytes. Biophys J 73:757–769

    Article  CAS  PubMed  Google Scholar 

  • Bechet D, Tassa A, Taillandier D, Combaret L, Attaix D (2005) Lysosomal proteolysis in skeletal muscle. Int J Biochem Cell Biol 37:2098–2114

    Article  CAS  PubMed  Google Scholar 

  • Bedner P, Steinhäuser C, Theis M (2011) Functional redundancy and compensation among members of gap junction protein families? Biochim Biophys Acta 1818:1971–1984

    PubMed  Google Scholar 

  • Berridge MJ (1993) Inositol trisphosphate, calcium signaling. Nature 361:315–325

    Article  CAS  PubMed  Google Scholar 

  • Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, Poueymirou WT, Panaro FJ, Na E, Dharmarajan K, Pan ZQ, Valenzuela DM, DeChiara TM, Stitt TN, Yancopoulos GD, Glass DJ (2001) Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294:1704–1708

    Article  CAS  PubMed  Google Scholar 

  • Braun T, Rudnicki MA, Arnold HH, Jaenish R (1992) Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell 71:369–382

    Article  CAS  PubMed  Google Scholar 

  • Bruzzone R, Dermietzel R (2006) Structure and function of gap junctions in the developing brain. Cell Tissue Res 326:239–248

    Article  CAS  PubMed  Google Scholar 

  • Bruzzone S, Guida L, Zocchi E, Franco L, De Flora A (2001) Connexin 43 hemichannels mediate Ca2+-regulated transmembrane NAD+ fluxes in intact cells. FASEB J 15:10–12

    CAS  PubMed  Google Scholar 

  • Bruzzone R, Hormuzdi SG, Barbe MT, Herb A, Monyer H (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci USA 100:13644–13649

    Article  CAS  PubMed  Google Scholar 

  • Bruzzone R, Barbe MT, Jakob NJ, Monyer H (2005) Pharmacological properties of homomeric and heteromeric pannexin hemichannels expressed in Xenopus oocytes. J Neurochem 92:1033–1043

    Article  CAS  PubMed  Google Scholar 

  • Buonanno A, Apone L, Morasso MI, Beers R, Brenner HR, Eftimie R (1992) The MyoD family of myogenic factors is regulated by electrical activity: isolation and characterization of a mouse Myf-5 cDNA. Nucleic Acids Res 20:539–544

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G (2007) Purine and pyrimidine receptors. Cell Mol Life Sci 64:1471–1483

    Article  CAS  PubMed  Google Scholar 

  • Buvinic S, Almarza G, Bustamante M, Casas M, López J, Riquelme M, Sáez JC, Huidobro-Toro JP, Jaimovich E (2009) ATP released by electrical stimuli elicits calcium transients and gene expression in skeletal muscle. J Biol Chem 284:34490–34505

    Article  CAS  PubMed  Google Scholar 

  • Cai D, Frantz JD, Tawa NE Jr, Melendez PA, Oh BC, Lidov HG, Hasselgren PO, Frontera WR, Lee J, Glass DJ, Shoelson SE (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119:285–298

    Article  CAS  PubMed  Google Scholar 

  • Callahan LA, Supinski GS (2009) Sepsis-induced myopathy. Crit Care Med 37:S354–S367

    Article  PubMed  Google Scholar 

  • Cao PR, Kim HJ, Lecker SH (2005) Ubiquitin-protein ligases in muscle wasting. Int J Biochem Cell Biol 37:2088–2097

    Article  CAS  PubMed  Google Scholar 

  • Casas M, Figueroa R, Jorquera G, Escobar M, Molgó J, Jaimovich E (2010) IP3-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers. J Gen Physiol 136:455–467

    Article  CAS  PubMed  Google Scholar 

  • Chargé SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238

    Article  PubMed  Google Scholar 

  • Cherian PP, Siller-Jackson AJ, Gu S, Wang X, Bonewald LF, Sprague E, Jiang JX (2005) Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol Biol Cell 16:3100–3106

    Article  CAS  PubMed  Google Scholar 

  • Coleman M (2005) Axon degeneration mechanisms: commonality amid diversity. Nat Rev Neurosci 6:889–898

    Article  CAS  PubMed  Google Scholar 

  • Contreras JE, Sánchez HA, Eugenin EA, Speidel D, Theis M, Willecke K, Bukauskas FF, Bennett MV, Sáez JC (2002) Metabolic inhibition induces opening of unapposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 99:495–500

    Article  CAS  PubMed  Google Scholar 

  • Cunha RA, Sebastião AM (1993) Adenosine and adenine nucleotides are independently released from both the nerve terminals and the muscle fibres upon electrical stimulation of the innervated skeletal muscle of the frog. Pflügers Arch 424:503–510

    Article  CAS  PubMed  Google Scholar 

  • D’Amico A, Mercuri E, Tiziano FD, Bertini E (2011) Spinal muscular atrophy. Orphanet J Rare Dis 6:71–81

    Article  PubMed  Google Scholar 

  • Dargelos E, Poussard S, Brule C, Daury L, Cottin P (2008) Calcium-dependent proteolytic system and muscle dysfunctions: a possible role of calpains in sarcopenia. Biochimie 90:359–368

    Article  CAS  PubMed  Google Scholar 

  • Davis MP, Dreicer R, Walsh D, Lagman R, LeGrand SB (2004) Appetite and cancer-associated anorexia: a review. J Clin Oncol 22:1510–1517

    Article  CAS  PubMed  Google Scholar 

  • Deli T, Szappanos H, Szigeti GP, Cseri J, Kovács L, Csernoch L (2007) Contribution from P2X and P2Y purinoreceptors to ATP-evoked changes in intracellular calcium concentration on cultured myotubes. Pflugers Arch 453:519–529

    Article  CAS  PubMed  Google Scholar 

  • Dennis MJ, Ziskind-Conhaim L, Harris AJ (1981) Development of neuromuscular junctions in rat embryos. Dev Biol 81:266–279

    Article  CAS  PubMed  Google Scholar 

  • Domercq M, Perez-Samartin A, Aparicio D, Alberdi E, Pampliega O, Matute C (2010) P2X7 receptors mediate ischemic damage to oligodendrocytes. Glia 58:730–740

    PubMed  Google Scholar 

  • Donoghue P, Ribaric S, Moran B, Cebasek V, Erzen I, Ohlendieck K (2004) Early effects of denervation on Ca2+-handling proteins in skeletal muscle. Int J Mol Med 13:767–772

    CAS  PubMed  Google Scholar 

  • Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, Price SR, Mitch WE (2004) Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest 113:115–123

    CAS  PubMed  Google Scholar 

  • Duxson MJ, Usson Y (1989) Cellular insertion of primary and secondary myotubes in embryonic rat muscles. Development 107:243–251

    CAS  PubMed  Google Scholar 

  • Dvoriantchikova G, Ivanov D, Panchin Y, Shestopalov VI (2006) Expression of pannexin family of proteins in the retina. FEBS Lett 580:2178–2182

    Article  CAS  PubMed  Google Scholar 

  • Escobar AL, Schinder AF, Biali FI, Nicola LC, Uchitel OD (1993) Potassium channels from normal and denervated mouse skeletal muscle fibers. Muscle Nerve 16:579–586

    Article  CAS  PubMed  Google Scholar 

  • Fearon KC (2011) Cancer cachexia and fat–muscle physiology. N Engl J Med 365:565–567

    Article  CAS  PubMed  Google Scholar 

  • Fearon KC, Barber MD, Moses AG (2001) The cancer cachexia syndrome. Surg Oncol Clin North Am 10:109–126

    CAS  Google Scholar 

  • Finol HJ, Lewis DM, Owens R (1981) The effects of denervation on contractile properties or rat skeletal muscle. J Physiol 319:81–92

    CAS  PubMed  Google Scholar 

  • Foletta VC, White LJ, Larsen AE, Léger B, Russell AP (2011) The role and regulation of MAFbx/atrogin-1 and MuRF1 in skeletal muscle atrophy. Pflugers Arch 461:325–335

    Article  CAS  PubMed  Google Scholar 

  • Foskett JK, White C, Cheung KH, Mak DO (2007) Inositol trisphosphate receptor Ca2+ release channels. Physiol Rev 87:593–658

    Article  CAS  PubMed  Google Scholar 

  • Friday BB, Pavlath GK (2001) A calcineurin- and NFAT-dependent pathway regulates Myf5 gene expression in skeletal muscle reserve cells. J Cell Sci 114:303–310

    CAS  PubMed  Google Scholar 

  • Gaietta G, Deerinck TJ, Adams SR, Bouwer J, Tour O, Laird DW, Sosinsky GE, Tsien RY, Ellisman MH (2002) Multicolor and electron microscopic imaging of connexin trafficking. Science 296:503–507

    Article  CAS  PubMed  Google Scholar 

  • Goldspink DF (1976) The effects of denervation on protein turnover of rat skeletal muscle. Biochem J 156:71–80

    CAS  PubMed  Google Scholar 

  • Goldspink DF (1978) The effects of denervation on protein turnover of the soleus and extensor digitorum longus muscles of adult mice. Comp Biochem Physiol B Biochem Mol Biol 61:37–41

    CAS  Google Scholar 

  • Goldspink DF, Garlick PJ, McNurlan MA (1983) Protein turnover measured in vivo and in vitro in muscles undergoing compensatory growth and subsequent denervation atrophy. Biochem J 210:89–98

    CAS  PubMed  Google Scholar 

  • Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL (2001) Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci USA 98:14440–14445

    Article  CAS  PubMed  Google Scholar 

  • Gorbe A, Becker DL, Dux L, Stelkovics E, Krenacs L, Bagdi E, Krenacs T (2005) Transient upregulation of connexin43 gap junctions and synchronized cell cycle control precede myoblast fusion in regenerating skeletal muscle in vivo. Histochem Cell Biol 123:573–583

    Article  CAS  PubMed  Google Scholar 

  • Gorbe A, Krenacs T, Cook JE, Becker DL (2007) Myoblast proliferation and syncytial fusion both depend on connexin43 function in transfected skeletal muscle primary cultures. Exp Cell Res 313:1135–1148

    Article  CAS  PubMed  Google Scholar 

  • Hale DE, Bennett MJ (1992) Fatty acid oxidation disorders: a new class of metabolic diseases. J Pediatr 121:1–11

    Article  CAS  PubMed  Google Scholar 

  • Hama T, Hirayama M, Hara T, Nakamura T, Atsuta N, Banno H, Suzuki K, Katsuno M, Tanaka F, Sobue G (2012) Discrimination of spinal and bulbar muscular atrophy from amyotrophic lateral sclerosis using sensory nerve action potentials. Muscle Nerve 45:169–174

    Article  PubMed  Google Scholar 

  • Helliwell TR, Wilkinson A, Griffiths RD, McClelland P, Palmer TE, Bone JM (1998) Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin. Neuropathol Appl Neurobiol 24:507–517

    Article  CAS  PubMed  Google Scholar 

  • Herridge MS, Cheung AM, Tansey CM, Matte-Martyn A, Diaz-Granados N, Al-Saidi F, Cooper AB, Guest CB, Mazer CD, Mehta S, Stewart TE, Barr A, Cook D, Slutsky AS (2003) One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348:683–693

    Article  PubMed  Google Scholar 

  • Hundal HS, Babij P, Watt PW, Ward MR, Rennie MJ (1990) Glutamine transport and metabolism in denervated rat skeletal muscle. Am J Physiol Endocrinol Metab 259:E148–E154

    CAS  Google Scholar 

  • Hussain H, Dudley GA, Johnson P (1987) Effects of denervation on calpain and calpastatin in hamster skeletal muscles. Exp Neurol 97:635–643

    Article  CAS  PubMed  Google Scholar 

  • Ishikawa M, Iwamoto T, Nakamura T, Doyle A, Fukumoto S, Yamada Y (2011) Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J Cell Biol 193:1257–1274

    Article  CAS  PubMed  Google Scholar 

  • Jiang S, Yuan H, Duan L, Cao R, Gao B, Xiong YF, Rao ZR (2011) Glutamate release through connexin 43 by cultured astrocytes in a stimulated hypertonicity model. Brain Res 1392:8–15

    Article  CAS  PubMed  Google Scholar 

  • Judge AR, Koncarevic A, Hunter RB, Liou HC, Jackman RW, Kandarian SC (2007) Role for IkappaBalpha, but not c-Rel, in skeletal muscle atrophy. Am J Physiol Cell Physiol 292:C372–C382

    Article  CAS  PubMed  Google Scholar 

  • Kalderon N, Epstein ML, Gilula NB (1977) Cell-to-cell communication and myogenesis. J Cell Biol 75:788–806

    Article  CAS  PubMed  Google Scholar 

  • Kandarian S (2008) The molecular basis of skeletal muscle atrophy—parallels with osteoporotic signaling. J Musculoskelet Neuronal Interact 8:340–341

    CAS  PubMed  Google Scholar 

  • Kennedy WR, Alter M, Sung JH, Sung JH (1968) Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology 18:671–680

    Article  CAS  PubMed  Google Scholar 

  • Kirby AC, Lindley BD (1981) Calcium content of rat fast and slow muscle after denervation. Comp Biochem Physiol A Physiol 70:583–586

    Article  Google Scholar 

  • Kollberg G, Moslemi A-R, Lindberg C, Holme E, Oldfors A (2005) Mitochondrial myopathy and rhabdomyolysis associated with a novel nonsense mutation in the gene encoding cytochrome c oxidase subunit I. J Neuropathol Exp Neurol 64:123–128

    CAS  PubMed  Google Scholar 

  • Kornegay JN, Childers MK, Bogan DJ, Bogan JR, Nghiem P, Wang J, Fan Z, Howard JF Jr, Schatzberg SJ, Dow JL, Grange RW, Styner MA, Hoffman EP, Wagner KR (2012) The paradox of muscle hypertrophy in muscular dystrophy. Phys Med Rehabil Clin N Am 23:149–172

    Article  PubMed  Google Scholar 

  • Kotsias BA, Venosa RA (2001) Sodium influx during action potential in innervated and denervated rat skeletal muscles. Muscle Nerve 24:1026–1033

    Article  CAS  PubMed  Google Scholar 

  • Lecker SH (2003) Ubiquitin-protein ligases in muscle wasting: multiple parallel pathways? Curr Opin Clin Nutr Metab Care 6:271–275

    CAS  PubMed  Google Scholar 

  • Legerlotz K, Smith HK (2008) Role of MyoD in denervated, disused, and exercised muscle. Muscle Nerve 38:1087–1100

    Article  CAS  PubMed  Google Scholar 

  • Lenman JA (1965) Effect of denervation on the resting membrane potential of healthy and dystrophic muscle. J Neurol Neurosurg Psychiatry 28:525–528

    Article  CAS  PubMed  Google Scholar 

  • Li H, Liu TF, Lazrak A, Peracchia C, Goldberg GS, Lampe PD, Johnson RG (1996) Properties and regulation of gap junctional hemichannels in the plasma membranes of cultured cells. J Cell Biol 134:1019–1030

    Article  CAS  PubMed  Google Scholar 

  • Li S, Bjelobaba I, Yan Z, Kucka M, Tomic M, Stojilkovic SS (2011) Expression and roles of pannexins in ATP release in the pituitary gland. Endocrinology 152:2342–2352

    Article  CAS  PubMed  Google Scholar 

  • Ling Y, Appelt D, Kelly AM, Franzini-Armstrong C (1992) Differences in the histogenesis of EDL and diaphragm in rat. Dev Dyn 193:359–369

    Article  CAS  PubMed  Google Scholar 

  • Locovei S, Bao L, Dahl G (2006a) Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci USA 103:7655–7659

    Article  CAS  PubMed  Google Scholar 

  • Locovei S, Wang J, Dahl G (2006b) Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 580:239–244

    Article  CAS  PubMed  Google Scholar 

  • Lomo T, Westgaard RH (1975) Further studies on the control of ACh sensitivity by muscle activity in the rat. J Physiol 252:603–626

    CAS  PubMed  Google Scholar 

  • Louboutin JP, Fichter-Gagnepain V, Noireaud J (1996) Effects of external calcium on contractile responses in rat extensor digitorum longus muscles after sciatic nerve injury at birth. Muscle Nerve 19:1421–1428

    Article  CAS  PubMed  Google Scholar 

  • Lu DX, Huang SK, Carlson BM (1997) Electron microscopic study of long-term denervated rat skeletal muscle. Anat Rec 248:355–365

    Article  CAS  PubMed  Google Scholar 

  • Lu D, Soleymani S, Madakshire R, Insel PA (2012) ATP released from cardiac fibroblasts via connexin hemichannels activates profibrotic P2Y2 receptors. FASEB J 26:2580–2591

    Article  CAS  PubMed  Google Scholar 

  • Marcreth A, Salviati G, Dimauro S, Turati G (1972) Early biochemical consequences of denervation of fast and slow skeletal muscles and their relationship in neural control over muscle differentiation. Biochem J 126:1099–1110

    Google Scholar 

  • Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M (2009) Autophagy is required to maintain muscle mass. Cell Metab 10:507–515

    Article  CAS  PubMed  Google Scholar 

  • May C, Weigl L, Karel A, Hohenegger M (2006) Extracellular ATP activates ERK1/ERK2 via a metabotropic P2Y1 receptor in a Ca2+ independent manner in differentiated human skeletal muscle cells. Biochem Pharmacol 71:1497–1509

    Article  CAS  PubMed  Google Scholar 

  • Meyer MP, Gröschel-Stewart U, Robson T, Burnstock G (1999) Expression of two ATP-gated ion channels, P2X5 and P2X6, in developing chick skeletal muscle. Dev Dyn 216:442–449

    Article  CAS  PubMed  Google Scholar 

  • Mikoshiba K (2007) IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. J Neurochem 102:1426–1446

    Article  CAS  PubMed  Google Scholar 

  • Molkentin JD, Olson EN (1996) Combinatorial control of muscle development by basic helix-loop-helix and MADS-box transcription factors. Proc Natl Acad Sci USA 93:9366–9367

    Article  CAS  PubMed  Google Scholar 

  • Moreno AP, Laing JG, Beyer EC, Spray DC (1995) Properties of gap junction channels formed of connexin 45 endogenously expressed in human hepatoma (SKHep1) cells. Am J Physiol Cell Physiol 268:C356–C365

    CAS  Google Scholar 

  • Moyle G (2005) Mechanisms of HIV and nucleoside reverse transcriptase inhibitor injury to mitochondria. Antivir Ther 10(Suppl 2):M47–M52

    CAS  PubMed  Google Scholar 

  • Müntener M, Berchtold MW, Heizmann CW (1985) Parvalbumin in cross-reinnervated and denervated muscles. Muscle Nerve 8:132–137

    Article  PubMed  Google Scholar 

  • Nagaraju K, Casciola-Rosen L, Lundberg I, Rawat R, Cutting S, Thapliyal R, Chang J, Dwivedi S, Mitsak M, Chen Y-W, Plotz P, Rosen A, Hoffman E, Raben N (2005) Activation of the endoplasmic reticulum stress response in autoimmune myositis: potential role in muscle fiber damage and dysfunction. Arthritis Rheum 52:1824–1835

    Article  CAS  PubMed  Google Scholar 

  • North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067

    CAS  PubMed  Google Scholar 

  • Okon EB, Golbabaie A, van Breemen C (2002) In the presence of L-NAME SERCA blockade induces endothelium-dependent contraction of mouse aorta through activation of smooth muscle prostaglandin H2/thromboxane A2 receptors. Br J Pharmacol 137:545–553

    Article  CAS  PubMed  Google Scholar 

  • Ontell M (1974) Muscle satellite cells: a validated technique for light microscopic identification and a quantitative study of changes in their population following denervation. Anat Rec 178:211–227

    Article  CAS  PubMed  Google Scholar 

  • Orellana JA, Hernández DE, Ezan P, Velarde V, Bennett MV, Giaume C, Sáez JC (2010) Hypoxia in high glucose followed by reoxygenation in normal glucose reduces the viability of cortical astrocytes through increased permeability of connexin 43 hemichannels. Glia 58:329–343

    PubMed  Google Scholar 

  • Orellana JA, Díaz E, Schalper KA, Vargas AA, Bennett MV, Sáez JC (2011) Cation permeation through connexin 43 hemichannels is cooperative, competitive and saturable with parameters depending on the permeant species. Biochem Biophys Res Commun 409:603–609

    Article  CAS  PubMed  Google Scholar 

  • Orellana JA, Sáez PJ, Cortés-Campos C, Elizondo RJ, Shoji KF, Contreras-Duarte S, Figueroa V, Velarde V, Jiang JX, Nualart F, Sáez JC, García MA (2012) Glucose increases intracellular free Ca2+ in tanycytes via ATP released through connexin 43 hemichannels. Glia 60:53–68

    Article  PubMed  Google Scholar 

  • Pangrsic T, Potokar M, Stenovec M, Kreft M, Fabbretti E, Nistri A, Pryazhnikov E, Khiroug L, Giniatullin R, Zorec R (2007) Exocytotic release of ATP from cultured astrocytes. J Biol Chem 282:28749–28758

    Article  CAS  PubMed  Google Scholar 

  • Peñuela S, Bhalla R, Gong XQ, Cowan KN, Celetti SJ, Cowan BJ, Bai D, Shao Q, Laird DW (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120:3772–3783

    Article  PubMed  CAS  Google Scholar 

  • Picken JR, Kirby AC (1976) Denervated frog skeletal muscle: Calcium content and kinetics of exchange. Exp Neurol 53:64–70

    Article  CAS  PubMed  Google Scholar 

  • Ponsaerts R, De Vuyst E, Retamal M, D’hondt C, Vermeire D, Wang N, De Smedt H, Zimmermann P, Himpens B, Vereecke J, Leybaert L, Bultynck G (2010) Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity. FASEB J 24:4378–4395

    Article  CAS  PubMed  Google Scholar 

  • Pownall ME, Gustafsson MK, Emerson CP Jr (2002) Myogenic regulatory factors and the specification of muscle progenitors in vertebrate embryos. Annu Rev Cell Dev Biol 18:747–783

    Article  CAS  PubMed  Google Scholar 

  • Pritschow BW, Lange T, Kasch J, Kunert-Keil C, Liedtke W, Brinkmeier H (2011) Functional TRPV4 channels are expressed in mouse skeletal muscle and can modulate resting Ca2+ influx and muscle fatigue. Pflugers Arch 461:115–122

    Article  CAS  PubMed  Google Scholar 

  • Proulx AA, Merrifield PA, Naus CC (1997) Blocking gap junctional intercellular communication in myoblasts inhibits myogenin and MRF4 expression. Dev Genet 20:133–144

    Article  CAS  PubMed  Google Scholar 

  • Račkauskas M, Neverauskas V, Skeberdis VA (2010) Diversity and properties of connexin gap junction channels. Medicina (Kaunas) 46:1–12

    Google Scholar 

  • Raff MC, Whitmore AV, Finn JT (2002) Axonal self-destruction and neurodegeneration. Science 296:868–871

    Article  CAS  PubMed  Google Scholar 

  • Ray A, Zoidl G, Wahle P, Dermietzel R (2006) Pannexin expression in the cerebellum. Cerebellum 5:189–192

    Article  CAS  PubMed  Google Scholar 

  • Retamal MA, Evangelista-Martínez F, León-Paravic CG, Altenberg GA, Reuss L (2011) Biphasic effect of linoleic acid on connexin 46 hemichannels. Pflugers Arch 461:635–643

    Article  CAS  PubMed  Google Scholar 

  • Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ (2001) Mediation of IGF-1-induced skeletal myotube hypertrophy by PI3K/Akt/mTOR and PI3K/Akt/GSK3 pathways. Nat Cell Biol 3:1009–1013

    Article  CAS  PubMed  Google Scholar 

  • Ropper AH (1992) The Guillain-Barré syndrome. N Engl J Med 326:1130–1136

    Article  CAS  PubMed  Google Scholar 

  • Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700

    Article  CAS  PubMed  Google Scholar 

  • Rudnicki MA, Schnegelsberg PN, Stead RH, Braun T, Arnold HH, Jaenisch R (1993) MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75:1351–1359

    Article  CAS  PubMed  Google Scholar 

  • Ruppelt A, Ma W, Borchardt K, Silberberg SD, Soto F (2001) Genomic structure, developmental distribution and functional properties of the chicken P2X5 receptor. J Neurochem 77:1256–1265

    Article  CAS  PubMed  Google Scholar 

  • Ryten M, Dunn PM, Neary JT, Burnstock G (2002) ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells. J Cell Biol 158:345–355

    Article  CAS  PubMed  Google Scholar 

  • Sacheck JM, Hyatt JP, Raffaello A, Jagoe RT, Roy RR, Edgerton VR, Lecker SH, Goldberg AL (2007) Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. FASEB J 21:140–155

    Article  CAS  PubMed  Google Scholar 

  • Sáez JC, Retamal MA, Basilio D, Bukauskas FF, Bennett MV (2005) Connexin-based gap junction hemichannels: gating mechanisms. Biochim Biophys Acta 1711:215–224

    Article  PubMed  CAS  Google Scholar 

  • Sánchez HA, Orellana JA, Verselis VK, Sáez JC (2009) Metabolic inhibition increases activity of connexin-32 hemichannels permeable to Ca2+ in transfected HeLa cells. Am J Physiol Cell Physiol 297:C665–C678

    Article  PubMed  CAS  Google Scholar 

  • Sánchez HA, Mese G, Srinivas M, White TW, Verselis VK (2010) Differentially altered Ca2+ regulation and Ca2+ permeability in Cx26 hemichannels formed by the A40 V and G45E mutations that cause keratitis ichthyosis deafness syndrome. J Gen Physiol 136:47–62

    Article  PubMed  CAS  Google Scholar 

  • Sandona D, Danieli-Betto D, Germinario E, Biral D, Martinello T, Lioy A, Tarricone E, Gastaldello S, Betto R (2005) The T-tubule membrane ATP-operated P2X4 receptor influences contractility of skeletal muscle. FASEB J 19:1184–1186

    CAS  PubMed  Google Scholar 

  • Schalper KA, Palacios-Prado N, Orellana JA, Sáez JC (2008) Currently used methods for identification and characterization of hemichannels. Cell Commun Adhes 15:207–218

    Article  CAS  PubMed  Google Scholar 

  • Schalper KA, Sánchez HA, Lee SC, Altenberg GA, Nathanson MH, Sáez JC (2010) Connexin 43 hemichannels mediate the Ca2+ influx induced by extracellular alkalinization. Am J Physiol Cell Physiol 299:C1504–C1515

    Article  CAS  PubMed  Google Scholar 

  • Schalper KA, Riquelme MA, Brañes MC, Martínez AD, Vega JL, Berthoud VM, Bennett MV, Sáez JC (2012) Modulation of gap junction channels and hemichannels by growth factors. Mol Biosyst 8:685–698

    Article  CAS  PubMed  Google Scholar 

  • Schmid A, Kazazoglou T, Renaud JF, Lazdunski M (1984) Comparative changes of levels of nitrendipine Ca2+ channels, of tetrodotoxin-sensitive Na+ channels and of ouabain-sensitive (Na+ + K+)-ATPase following denervation of rat and chick skeletal muscle. FEBS Lett 172:114–118

    Article  CAS  PubMed  Google Scholar 

  • Shea L, Raben N (2009) Autophagy in skeletal muscle: implications for Pompe disease. Int J Clin Pharmacol Ther 47(Suppl 1):S42–S47

    CAS  PubMed  Google Scholar 

  • Shimizu S, Kuriaki K (1960) Effect of denervation on the total metal content of skeletal muscle. Am J Physiol 198:943–944

    CAS  PubMed  Google Scholar 

  • Smith OL, Wong CY, Gelfand RA (1989) Skeletal muscle proteolysis in rats with acute streptozocin-induced diabetes. Diabetes 38:1117–1122

    Article  CAS  PubMed  Google Scholar 

  • Snow MH (1983) A quantitative ultrastructural analysis of satellite cells in denervated fast and slow muscles of the mouse. Anat Rec 207:593–604

    Article  CAS  PubMed  Google Scholar 

  • Sobue G, Hashizume Y, Mukai E, Hirayama M, Mitsuma T, Takahashi A (1989) X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain 112:209–232

    Article  PubMed  Google Scholar 

  • Söhl G, Willecke K (2004) Gap junctions and the connexin protein family. Cardiovasc Res 62:228–232

    Article  PubMed  CAS  Google Scholar 

  • Solan JL, Lampe PD (2009) Connexin43 phosphorylation: structural changes and biological effects. Biochem J 419:261–272

    Article  CAS  PubMed  Google Scholar 

  • Sonobe T, Inagaki T, Poole DC, Kano Y (2008) Intracellular calcium accumulation following eccentric contractions in rat skeletal muscle in vivo: role of stretch-activated channels. Am J Physiol Regul Integr Comp Physiol 294:R1329–R1337

    Article  CAS  PubMed  Google Scholar 

  • Sosinsky GE, Boassa D, Dermietzel R, Duffy HS, Laird DW, MacVicar B, Naus CC, Penuela S, Scemes E, Spray DC, Thompson RJ, Zhao HB, Dahl G (2011) Pannexin channels are not gap junction hemichannels. Channels 5:193–197

    Article  CAS  PubMed  Google Scholar 

  • Steinberg TH, Civitelli R, Geist ST, Robertson AJ, Hick E, Veenstra RD, Wang HZ, Warlow PM, Westphale EM, Laing JG (1994) Connexin43 and connexin45 form gap junctions with different molecular permeabilities in osteoblastic cells. EMBO J 13:744–750

    CAS  PubMed  Google Scholar 

  • Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science 312:924–927

    Article  CAS  PubMed  Google Scholar 

  • Tisdale MJ (2008) Catabolic mediators of cancer cachexia. Curr Opin Support Palliat Care 2:256–261

    Article  PubMed  Google Scholar 

  • Treem WR (2000) New developments in the pathophysiology, clinical spectrum, and diagnosis of disorders of fatty acid oxidation. Curr Opin Pediatr 12:463–468

    Article  CAS  PubMed  Google Scholar 

  • Vanden Abeele F, Bidaux G, Gordienko D, Beck B, Panchin YV, Baranova AV, Ivanov DV, Skryma R, Prevarskaya N (2006) Functional implications of calcium permeability of the channel formed by pannexin 1. J Cell Biol 174:535–546

    Article  CAS  PubMed  Google Scholar 

  • Vary TC, Kimball SR (1992) Sepsis-induced changes in protein synthesis: differential effects on fast- and slow-twitch muscles. Am J Physiol Cell Physiol 262:C1513–C1519

    CAS  Google Scholar 

  • Ventadour S, Attaix D (2006) Mechanisms of skeletal muscle atrophy. Curr Opin Rheumatol 18:631–635

    Article  CAS  PubMed  Google Scholar 

  • von Maltzahn J, Euwens C, Willecke K, Sohl G (2004) The novel mouse connexin39 gene is expressed in developing striated muscle fibers. J Cell Sci 117:5381–5392

    Article  CAS  Google Scholar 

  • von Maltzahn J, Wulf V, Willecke K (2006) Spatiotemporal expression of connexin 39 and -43 during myoblast differentiation in cultured cells and in the mouse embryo. Cell Commun Adhes 13:55–60

    Article  CAS  Google Scholar 

  • von Maltzahn J, Wulf V, Matern G, Willecke K (2011) Connexin39 deficient mice display accelerated myogenesis and regeneration of skeletal muscle. Exp Cell Res 317:1169–1178

    Article  CAS  Google Scholar 

  • Wang J, Ma M, Locovei S, Keane RW, Dahl G (2007) Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol 293:C1112–C1119

    Article  CAS  PubMed  Google Scholar 

  • Wanke CA, Silva M, Knox TA, Forrester J, Speigelman D, Gorbach SL (2000) Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 3:803–805

    Article  Google Scholar 

  • Weintraub H (1993) The MyoD family and myogenesis: redundancy, networks, and thresholds. Cell 75:1241–1244

    Article  CAS  PubMed  Google Scholar 

  • Winlow W, Usherwood PN (1975) Ultrastructural studies of normal and degenerating mouse neuromuscular junctions. J Neurocytol 4:377–394

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Fritz N, Ibarra C, Uhlén P (2011) Inositol 1,4,5-trisphosphate receptor subtype-specific regulation of calcium oscillations. Neurochem Res 36:1175–1185

    Article  CAS  PubMed  Google Scholar 

  • Zhi G, Ryder JW, Huang J, Ding P, Chen Y, Zhao Y, Kamm KE, Stull JT (2005) Myosin light chain kinase and myosin phosphorylation effect frequency-dependent potentiation of skeletal muscle contraction. Proc Natl Acad Sci USA 102:17519–17524

    Article  CAS  PubMed  Google Scholar 

  • Zhou X, Wang JL, Lu J, Song Y, Kwak KS, Jiao Q, Rosenfeld R, Chen Q, Boone T, Simonet WS, Lacey DL, Goldberg AL, Han HQ (2010) Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 142:531–543

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departamento de Fisiología, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile

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

  2. Centro Interdisciplinario de Neurociencias de Valparaíso, Valparaiso, Chile

    Carlos Puebla & Juan C. Sáez

  3. Laboratorio de Fisiología Experimental, Universidad de Antofagasta, Antofagasta, Chile

    José L. Vega

Authors
  1. Luis A. Cea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Manuel A. Riquelme
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bruno A. Cisterna
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos Puebla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. José L. Vega
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maximiliano Rovegno
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juan C. Sáez
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan C. Sáez.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cea, L.A., Riquelme, M.A., Cisterna, B.A. et al. Connexin- and Pannexin-Based Channels in Normal Skeletal Muscles and Their Possible Role in Muscle Atrophy. J Membrane Biol 245, 423–436 (2012). https://doi.org/10.1007/s00232-012-9485-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00232-012-9485-8

Keywords

Search

Navigation