Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

摘要

The CD-1 mouse strain is known to have early onset of hearing loss that is progressive with aging. We sought to determine whether a disturbance of K⁺ homeostasis and pathological changes in the cochlear lateral wall were involved in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain which has minimal AHL. In the present study, the endocochlear potential (EP) and endolymphatic K⁺ concentration ([K⁺]e) were measured in both strains of mice with double-barrel microelectrodes at “young” (1–2 mo) and “old” (5–9 mo) ages. CBA/CaJ mice displayed no changes with aging in EP and [K⁺]e of the basal turn. In the apical turn, there was a small positive shift of the EP (10 mV) with aging under both normoxic and acute anoxic conditions (−EP), without any change of [K⁺]e. Further, there were no obvious pathological changes in the lateral wall of CBA/CaJ mice. By contrast, old CD-1 mice displayed a significantly reduced [K⁺]e by 30% in both basal and apical turns with no significant changes in normoxic EP. The −EP in the apical turn was significantly reduced in magnitude by 6 mV. A severe loss of cells with aging was observed in the region of type IV fibrocytes of the apical and basal turns and of type II fibrocytes in the basal turn. A complete degeneration of organ of Corti was also observed at the basal turn of old CD-1 mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-1 mice were similar to those of an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a primary etiology of AHL of CD-1 mice. These findings have ramifications for our understanding of AHL and for interpretation of genetic mutations in a CD-1 background.