title: Differential effects of pannexins on noise-induced hearing loss.
abstract: Hearing loss, including noise-induced hearing loss, is highly prevalent and severely hinders an individual's quality of life, yet many of the mechanisms that cause hearing loss are unknown. The pannexin (Panx) channel proteins, Panx1 and Panx3, are regionally expressed in many cell types along the auditory pathway, and mice lacking Panx1 in specific cells of the inner ear exhibit hearing loss, suggesting a vital role for Panxs in hearing. We proposed that Panx1 and/or Panx3 null mice would exhibit severe hearing loss and increased susceptibility to noise-induced hearing loss. Using the auditory brainstem response, we surprisingly found that Panx1-/-and Panx3-/-mice did not harbor hearing or cochlear nerve deficits. Furthermore, while Panx1-/-mice displayed no protection against loud noise-induced hearing loss, Panx3-/-mice exhibited enhanced 16- and 24-kHz hearing recovery 7 days after a loud noise exposure (NE; 12 kHz tone, 115 dB sound pressure level, 1 h). Interestingly, Cx26, Cx30, Cx43, and Panx2 were up-regulated in Panx3-/-mice compared with wild-type and/or Panx1-/-mice, and assessment of the auditory tract revealed morphological changes in the middle ear bones of Panx3-/-mice. It is unclear if these changes alone are sufficient to provide protection against loud noise-induced hearing loss. Contrary to what we expected, these data suggest that Panx1 and Panx3 are not essential for baseline hearing in mice tested, but the therapeutic targeting of Panx3 may prove protective against mid-high-frequency hearing loss caused by loud NE.
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors: Julia M
authors: JM
authors: Abitbol
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors: John J
authors: JJ
authors: Kelly
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors: Kevin
authors: K
authors: Barr
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors: Ashley L
authors: AL
authors: Schormans
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors: Dale W
authors: DW
authors: Laird
authors: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors: Brian L
authors: BL
authors: Allman
mesh_terms: D000818:Animals; D003051:Cochlea / Q000378:metabolism / Q000502:physiology; D000072259:Connexin 26; D000075302:Connexin 30; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000235:genetics / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C000607043:Gjb2 protein, mouse; C100629:Gjb6 protein, mouse; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; C516139:Panx2 protein, mouse; C528477:pannexin 3 protein, mouse; D000072259:Connexin 26
keywords: auditory brainstem response; hearing; mouse; noise-induced hearing loss; pannexins