title: Simultaneously reduced NKCC1 and Na,K-ATPase expression in murine cochlear lateral wall contribute to conservation of endocochlear potential following a sensorineural hearing loss.
abstract: The mechanisms of the response in the murine cochlear lateral wall following sensorineural hearing loss (SNHL) are poorly understood. We focused on comparing the endocochlear potential (EP) with morphological changes in the lateral wall and expression of four important potassium (K(+)) transporters in a mouse model of SNHL induced by co-administration of aminoglycoside and loop diuretic. The expression of the α1 and α2 isoforms of Na,K-ATPase, Na-K-2Cl-Cotransporter-1 (NKCC1) and potassium channel KCNQ1 was assessed. The EP showed a significant decline at 12h post-treatment followed by complete recovery by 2 days post-treatment. The EP was maintained at near normal levels in animals deafened for periods up to 112 days. Despite this recovery, there was a significant and progressive decrease in the thickness of the stria vascularis, which was predominantly due to atrophy of marginal cells. Both protein and mRNA expression of α1 and α2 isoforms of Na,K-ATPase and NKCC1 in the lateral wall were dramatically reduced following a long-term deafening. KCNQ1 expression remained unchanged. These observations provide insight into the detailed mechanisms of EP modulation following SNHL and may have crucial implications in the future treatment of aminoglycoside-induced hearing loss.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xiong
authors.forename: Hanqi
authors.initials: H
authors.lastname: Chu
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Huang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Cui
authors.forename: Liangqiang
authors.initials: L
authors.lastname: Zhou
authors.forename: Jin
authors.initials: J
authors.lastname: Chen
authors.forename: Jianling
authors.initials: J
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Chen
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D003051:Cochlea / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005072:Evoked Potentials, Auditory / Q000502:physiology; D006319:Hearing Loss, Sensorineural / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D046529:Microscopy, Electron, Transmission; D020133:Reverse Transcriptase Polymerase Chain Reaction; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis*; D064506:Solute Carrier Family 12, Member 2; D013316:Stria Vascularis / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C578878:Slc12a2 protein, mouse; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; C401838:Atp1a2 protein, mouse; C497344:Atp1a1 protein, mouse; D000254:Sodium-Potassium-Exchanging ATPase