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.
Highlights
Pendrin is an anion exchanger that transports intracellular HCO3, I, and formate to the extracellular space in exchange for Cl- [1,2,3]
The inner ear is composed of luminal space, which is surrounded by epithelial cells with tight junctions, and abluminal space between the luminal space and surrounding bone (Fig. 1)
Such stretching of the inner ear epithelium can cause the loss of endocochlear potential by the degeneration of the stria vascularis, which causes the loss of hearing [6,7]
Summary
Pendrin is an anion exchanger that transports intracellular HCO3-, I-, and formate to the extracellular space in exchange for Cl- [1,2,3]. Pendrin is distributed to the following specific parts of the non-sensory epithelium of the membranous labyrinth: the spiral prominence, root cells, and spindle cells of the cochlea, vestibular transitional cells, and the endolymphatic sac epithelium [4,5]. The selective disruption of pendrin in mice causes the dilation of the membranous labyrinth (endolymphatic hydrops) beginning at 14.5 embryonic days, which can stretch the inner ear epithelial cells. Such stretching of the inner ear epithelium can cause the loss of endocochlear potential by the degeneration of the stria vascularis, which causes the loss of hearing [6,7]. The exact mechanism for the development of endolymphatic hydrops is not well understood, it has been proposed that the acidification of endolymph causes a decrease in the H+-ATPase function in the endolymphatic sac, which results in decreased Na+ absorption through ENaC and causes endolymphatic hydrops [9]
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