More details
Hide details
Department of Otolaryngology, Uppsala University Hospital, Uppsala, Sweden
Publication date: 2011-09-30
Corresponding author
Wei Liu   

Wei Liu, Department of Surgical Sciences, Section of Otolaryngology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden, Phone: +46-18-6115456, e-mail: lwoo24@gmail.com
Helge Rask-Andersen   

Helge Rask-Andersen and Wei Liu, Department of Surgical Sciences, Section of Otolaryngology, Uppsala University Hospital, SE-751 85 Uppsala, Sweden, Phone: +46-18-6115456, e-mail: helge.rask-andersen@akademiska.se
J Hear Sci 2011;1(3):21-29
Mutations in the gene GJA1 which encodes gap junction protein connexin 43 (Cx43) have been linked to nonsyndromic prelingual deafness in humans. The protein forms gap junction channels (GJChs), creating intercellular pathways for ions and small molecules – such as second messengers (IP3, cAMP, cGMP, and others), diverse metabolites (e.g. glucose, amino acids, glutathione, ATP) and neuroprotectant (e.g. adenosine) – to reach neighboring cells. Cx43 in glial cells of the central nervous system (CNS) and in satellite glial cells of the peripheral nociceptive sensory ganglia has been studied for its structure as well as function in signal transduction and neuron protection. Distribution of Cx43 in the human cochlea is an important unresolved issue.

Material and Methods:
For the first time we analysed, using immunofluorescence and confocal immunofluorescence, the expression and distribution of Cx43 in 5 normal fresh human cochleae obtained at surgery for removal of giant posterior cranial fossa meningioma.

In the lateral wall of the cochlea, Cx43 was expressed mainly in the basal cell layer of the stria vascularis and the fibrocytes of the spiral ligament. In the organ of Corti, Cx43 antibody strongly stained both inner and outer pillar cells, the covering layer cells of the basilar membrane and the supporting cells underneath outer hair cells. In the spiral ganglion, Cx43 expression was located in the satellite glial cells (SGCs) surrounding type I neurons.

Cx43 expression was found in human cochleae including the lateral wall, organ of Corti and spiral ganglion satellite cells. Potential roles played by GJChs built up by Cx43 in maintaining homeostasis of the cochlea and protection of neurons are speculated.

Sohl G, Willecke K: Gap junctions and the connexin protein family. Cardiovascular Research, 2004; 62: 228–32.
Kandel ER, Michael VL: Bennett and the cellular study of neural systems at Albert Einstein and Woods Hole. Brain Res, 2000; 32: 3–5.
Hormuzdi SG, Filippov MA, Mitropoulou G et al: Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks. Biochim Biophys Acta, 2004; 1662: 113–37.
Bennett MV, Zukin RS: Electrical coupling and neuronal synchronization in the mammalian brain. Neuron, 2004; 41: 495–511.
Kelsell DP, Dunlop J, Stevens HP et al: Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature, 1997; 387: 80–83.
Cohn ES, Kelley PM: Clinical phenotype and mutations in connexin 26 (DFNB1/GJB2), the most common cause of childhood hearing loss. Am J Med Genet, 1999; 89: 130–36.
Martínez AD, Acuna R, Figueroa V et al: Gap-Junction Channels Dysfunction in Deafness and Hearing Loss. Aantioxidant & Redox Signaling, 2009; 11: 309–22.
Liu XZ, Xia XJ, Adams J et al: Mutations in GJA1 (connexin 43) are associated with non-syndromic autosomal recessive deafness. Hum Mol Genet, 2001; 10: 2945–51.
Yang JJ, Huang SH, Chou KH et al: Identification of mutations in members of the connexin gene family as a cause of nonsyndromic deafness in Taiwan. Audiol Neurootol, 2007; 12: 198–208.
Corcos IA, Meese EU, Loch-Caruso R: Human connexin 43 gene locus, GJA1, sublocalized to band 6q21!q23.2. Cytogenet Cell Genet, 1993; 64: 31–32.
Houades V, Koulakoff A, Ezan P, Seif I, Giaume C: Gap junction-mediated astrocytic networks in the mouse barrel cortex. J Neurosci, 2008; 28: 5207–17.
Cotrina ML, Gao Q, Lin JH, Nedergaard M: Expression and function of astrocytic gap junctions in aging. Brain Res, 2001; 901: 55–61.
Yamamoto T, Ochalski A, Hertzberg EL, Nagy JI: On the organization of astrocytic gap junctions in rat brain as suggested by LM and EM immunohistochemistry of connexin43 expression. J Comp Neurol, 1990; 302: 853–83.
Vit JP, Jasmin L, Bhargava A, Ohara PT: Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain. Neuron Glia Biol, 2006; 2: 247–57.
Procacci P, Magnaghi V, Pannese E: Perineuronal satellite cells in mouse spinal ganglia express the gap junction protein connexin43 throughout life with decline in old age. Brain Research Bulletin, 2008; 75: 562–69.
Paznekas WA, Boyadjiev SA, Shapiro RE et al: Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet, 2003; 72: 408–18.
Liu W, Boström M, Kinnefors A, Rask-Andersen H. Unique expression of connexins in the human cochlea. Hear Res, 2009; 250: 55–62.
Kammen-Jolly K, Ichiki H, Scholtz AW et al: Connexin 26 in human fetal development of the inner ear. Hear Res 2001; 160: 15–21.
Suzuki T, Takamatsu T, Oyamada M: Expression of gap junction protein connexin43 in the adult rat cochlea: comparison with connexin26. J Histochem Cytochem, 2003; 51: 903–12.
Cohen-Salmon M, Maxeiner S, Krüger O et al: Expression of the connexin43- and connexin45-encoding genes in the developing and mature mouse inner ear. Cell Tissue Res, 2004; 316: 15–22.
Nadol JB Jr: Comparative anatomy of the cochlea and auditory nerve in mammals. Hear Res, 1988; 34: 253–66.
Nadol JB Jr: Degeneration of cochlear neurons as seen in the spiral ganglion of man. Hear Res, 1990; 49: 141–54.
Spoendlin H, Schrott A: Quantitative evaluation of the human cochlear nerve. Acta Otolaryngol Suppl, 1990; 470: 61–69.
Tylstedt S, Kinnefors A, Rask-Andersen H: Neural interaction in the human spiral ganglion: a TEM study. Acta Otolaryngol, 1997; 117: 505–12.
Glueckert R, Pfaller K, Kinnefors A et al: The human spiral ganglion: new insights into ultrastructure, survival rate and implications for cochlear implants. Audiol Neurootol, 2005; 10: 258–73.
Liu W, Boström M, Kinnefors A et al: Expression of myelin basic protein in the human auditory nerve-An immunohistochemical and comparative study. Auris Nasus Larynx, 2011; May 19. Early Online Publication.
Kikuchi T, Kimura RS, Paul DL, Adams JC: Gap junctions in the rat cochlea: immunohistochemical and ultrastructural analysis. Anat Embryol 1995; 191: 101–18.
Cohen-Salmon M, Ott T, Michel V et al: Targeted ablation of connexin26 in the inner ear epithelial gap junction network causes hearing impairment and cell death. Curr Biol, 2002; 12: 1106–11.
Hernandez VH, Bortolozzi M, Pertegato V et al: Unitary permeability of gap junction channels to second messengers measured by FRET microscopy. Nat Methods, 2007; 4: 353–58.
Linthicum FH Jr, Fayad JN: Spiral ganglion cell loss is unrelated to segmental cochlear sensory system degeneration in humans. Otol Neurotl, 2009; 30: 418–22.
Statuto M, Bianchi C, Perego R, Monte UD: Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a possible biomarker of senescence. Exp Gerontol, 2002; 37: 1113–20.
Hong HM, Yang JJ, Shieh JQ et al: Novel mutations in the connexin43 (GJA1) and GJA1 pseudogene may contribute to nonsyndromic hearing loss. Hum Genet, 2010; 127: 545–51.
Journals System - logo
Scroll to top