PMID- 27784763 OWN - NLM STAT- MEDLINE DCOM- 20170612 LR - 20220129 IS - 1470-8728 (Electronic) IS - 0264-6021 (Linking) VI - 473 IP - 24 DP - 2016 Dec 15 TI - Differential effects of pannexins on noise-induced hearing loss. PG - 4665-4680 AB - 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. CI - (c) 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society. FAU - Abitbol, Julia M AU - Abitbol JM AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. FAU - Kelly, John J AU - Kelly JJ AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. FAU - Barr, Kevin AU - Barr K AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. AD - Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada. FAU - Schormans, Ashley L AU - Schormans AL AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. FAU - Laird, Dale W AU - Laird DW AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. AD - Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada. FAU - Allman, Brian L AU - Allman BL AD - Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario N6A 5C1, Canada. LA - eng GR - F40/ACT_/RNID/United Kingdom GR - 130530/CIHR/Canada GR - 148584/CIHR/Canada GR - 137098/CIHR/Canada PT - Journal Article DEP - 20161026 PL - England TA - Biochem J JT - The Biochemical journal JID - 2984726R RN - 0 (Connexin 30) RN - 0 (Connexin 43) RN - 0 (Connexins) RN - 0 (Gjb2 protein, mouse) RN - 0 (Gjb6 protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Panx1 protein, mouse) RN - 0 (Panx2 protein, mouse) RN - 0 (pannexin 3 protein, mouse) RN - 127120-53-0 (Connexin 26) SB - IM MH - Animals MH - Cochlea/metabolism/physiology MH - Connexin 26 MH - Connexin 30 MH - Connexin 43/metabolism MH - Connexins/genetics/*metabolism MH - Evoked Potentials, Auditory, Brain Stem/genetics/physiology MH - Hearing Loss, Noise-Induced/genetics/*metabolism MH - Immunoblotting MH - Mice MH - Mice, Knockout MH - Nerve Tissue Proteins/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction OTO - NOTNLM OT - auditory brainstem response OT - hearing OT - mouse OT - noise-induced hearing loss OT - pannexins EDAT- 2016/10/28 06:00 MHDA- 2017/06/13 06:00 CRDT- 2016/10/28 06:00 PHST- 2016/07/11 00:00 [received] PHST- 2016/10/14 00:00 [revised] PHST- 2016/10/24 00:00 [accepted] PHST- 2016/10/28 06:00 [pubmed] PHST- 2017/06/13 06:00 [medline] PHST- 2016/10/28 06:00 [entrez] AID - BCJ20160668 [pii] AID - 10.1042/BCJ20160668 [doi] PST - ppublish SO - Biochem J. 2016 Dec 15;473(24):4665-4680. doi: 10.1042/BCJ20160668. Epub 2016 Oct 26.