Abstract
The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (P D) and osmotic (P f) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The P D of the entire CDE (P D = 8.18 × 10−5 cm s−1) and its individual partitions including Reissner's membrane (P D = 12.06 × 10−5 cm s−1) and the organ of Corti (P D = 10.2 × 10−5 cm s−1) were similar to other epithelia with AQP-facilitated water permeation. The P f of the CDE (P f = 6.15 × 10−4 cm s−1) was also in the range of other epithelia while an exceptionally high P f was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; P f = 156.90 × 10−3 cm s−1). The P f/P D ratios of the CDE (P f/P D = 7.52) and OSCs (P f/P D = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or “water shunt” in the cochlear apex. This “water shunt” explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease.
Highlights
The inner ear is a fluid-filled sensory organ enclosing two unique extracellular fluids, perilymph and endolymph
Water permeability coefficients for the entire cochlear duct epithelium (CDE), Reissner's membrane (RM) and OC were determined in this study based on previously derived in vivo experimental data on the diffusive [44] and osmotic water exchange [78] across these epithelial boundaries in the guinea pig cochlea
Four lines of evidence (1–4) reveal the physiological relevance of AQP-mediated perilymphatic–endolymphatic water exchange in the mammalian cochlea: 1. Quantitative comparison of P D and P f for the entire cochlear duct epithelium yields water permeability coefficients in the same range seen in epithelia with aquaporin-facilitated water permeation A comparison of P D (8.18×10−5 cm s−1) and P f (6.15×10−4 cm s−1) for the entire CDE with water permeability coefficients reported for various other AQPexpressing epithelia revealed that these values were of the same order of magnitude while non-AQP-expressing cells demonstrate much lower values (Fig. 8)
Summary
The inner ear is a fluid-filled sensory organ enclosing two unique extracellular fluids, perilymph and endolymph. Several transmembrane proteins have been identified in the CDE that facilitate the transepithelial exchange of K+, Na+ and Cl−, consistent with the high electrolyte permeability of the cochlear PEB [reviewed in 51]). P D is a measure of the rate of water exchange across an interface (per unit area) based on thermal movements in the absence of an osmotic or hydrostatic gradient. As a quantitative and comparative measure, P D and P f have been determined for various AQP-expressing epithelia (reviewed in [96]); despite the established, abundant expression of AQPs in the CDE, PD and Pf have not been established for this epithelium, and the functional significance of AQPs in transepithelial water exchange between the cochlear perilymph and endolymph remains unknown
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