title: Developmental changes of ENaC expression and function in the inner ear of pendrin knock-out mice as a perspective on the development of endolymphatic hydrops.
abstract: Pendrin mutations cause enlarged vestibular aqueducts and various degrees of sensorineural hearing loss. The selective abolition of pendrin causes dilation of the membranous labyrinth known as endolymphatic hydrops, loss of the endocochlear potential, and consequently loss of hearing function. Because Na+ transport is one of the most important driving forces for fluid transport, the epithelial Na+ channel (ENaC) is believed to play an important role in fluid volume regulation in the inner ear. Therefore, the dysfunction of Na+ transport through ENaC by the acidification of endolymph in Pendred syndrome is one of the potential causes of endolymphatic hydrops. We investigated the changes of ENaC expression and function during the development of the pendrin knock-out mouse. In the cochlea, the expression of β and γENaC was significantly increased at P56 in Pds-/- mice compared with Pds+/+ mice. In the vestibule, the expression of βENaC was significantly increased at P56, and γENaC expression significantly increased from P6 to P56 in Pds-/- mice. The ENaC-dependent trans-epithelial current was not significantly different between Pds+/+ and Pds-/- mice in Reissner's membrane or the saccular extramacular roof epithelium at P0, but the current was significantly increased in Pds-/- mice at P56 compared with Pds+/+ mice. These findings indicate that the expression and function of ENaC were enhanced in Pds-/- mice after the development of endolymphatic hydrops as a compensatory mechanism. This result provides insight into the role of Na+ transport in the development and regulation of endolymphatic hydrops due to pendrin mutations.
authors.affiliation: Department of Otorhinolaryngology, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Bo Gyung
authors.initials: BG
authors.lastname: Kim
authors.affiliation: Research Center for Natural Human Defense System, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Otology, Hana ENT Hospital, Seoul, Korea.
authors.forename: Hee Nam
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Jinwoong
authors.initials: J
authors.lastname: Bok
authors.affiliation: College of Pharmacy, Yonsei institute of Pharmaceutical Sciences, Yonsei University, Incheon, Korea.
authors.forename: Wan
authors.initials: W
authors.lastname: Namkung
authors.affiliation: Department of Otorhinolaryngology, Yonsei University, College of Medicine, Seoul, Korea; Research Center for Natural Human Defense System, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Otorhinolaryngology, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Sung Huhn
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D007758:Ear, Inner / Q000378:metabolism*; D018159:Endolymphatic Hydrops / Q000235:genetics / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000076988:Sulfate Transporters
chemical_list: D027321:Anion Transport Proteins; D053503:Epithelial Sodium Channels; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters
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