Time course of inner ear degeneration and deafness in mice lacking the Kir4.1 potassium channel subunit

• Published in: Hearing research Vol. 177; no. 1; pp. 71 - 80
• Main Authors: Rozengurt, Nora, Lopez, Ivan, Chiu, Chi-Sung, Kofuji, Paulo, Lester, Henry A, Neusch, Clemens
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2003; Elsevier
• Subjects: Animals; Behavior, Animal; Biological and medical sciences; Cochlear Duct - pathology; Deafness; Deafness - etiology; Deafness - pathology; Deafness - physiopathology; Development; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ear, Inner - metabolism; Ganglia - pathology; Inner ear; Inwardly rectifying K + channel; KCNJ10; Labyrinth Diseases - etiology; Labyrinth Diseases - pathology; Labyrinth Diseases - physiopathology; Medical sciences; Mice; Mice, Knockout; Nerve Degeneration - pathology; Neurons - pathology; Non tumoral diseases; Otorhinolaryngology. Stomatology; Potassium Channels, Inwardly Rectifying - deficiency; Potassium Channels, Inwardly Rectifying - metabolism; Reflex, Startle; Spiral Ganglion - pathology; Stria vascularis; Time Factors; Vestibule, Labyrinth - innervation; Deafness; KCNJ10; Inwardly rectifying K + channel; Development; Stria vascularis; ITI, inter-trial interval; PPI, pre-pulse inhibition; EP, endocochlear potential; Inner ear; Kir4.1 potassium channel; Inwardly rectifying K+ channel; Auditory disorder; Ionic channel; Ionic current; Subunit; ENT disease; Degeneration; Hair cell of the ear; Internal ear disease; Rodentia; Gene expression; Hearing loss; Vertebrata; Mammalia; Mouse; Animal; Cochlea; Mutation; Potassium
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/S0378-5955(02)00799-2

The Kir4.1 gene (KCNJ10) encodes an inwardly rectifying K + channel subunit abundantly expressed in the CNS. Its expression in the mammalian inner ear has been suggested but its function in vivo in the inner ear is unknown. Because diverse human hereditary deafness syndromes are associated with mutations in K + channels, we examined auditory function and inner ear structure in mice with a genetically inactivated Kir4.1 K + channel subunit. Startle response experiments suggest that Kir4.1−/− mice are profoundly deaf, whereas Kir4.1+/− mice react like wild-type mice to acoustic stimuli. In Kir4.1−/− mice, the Reissner membrane is collapsed, the tectorial membrane is swollen, and type I hair cells and spiral ganglion neurons as well as their central processes degenerate over the first postnatal weeks. In the vestibular ganglia, neuronal cell death with apoptotic features is also observed. Immunostaining reveals that Kir4.1 is strongly expressed in stria vascularis of wild-type but not Kir4.1−/− mice. Within the spiral ganglion, Kir4.1 labeling was detected on satellite cells surrounding spiral ganglion neurons and axons. We conclude that Kir4.1 is crucial for normal development of the cochlea and hearing, via two distinct aspects of extracellular K + homeostasis: (1) in stria vascularis, Kir4.1 helps to generate the cochlear endolymph; and (2) in spiral and vestibular ganglia, Kir4.1 in surrounding glial cells helps to support the spiral and vestibular ganglion neurons and their projecting axons.