Lang Florian, Vallon Volker, Knipper Marlies, Wangemann Philine
Department of Physiology, Eberhard-Karls-University of Tübingen, Gmelinstrasse 5, Tübingen, Germany.
Am J Physiol Cell Physiol. 2007 Oct;293(4):C1187-208. doi: 10.1152/ajpcell.00024.2007. Epub 2007 Aug 1.
A number of ion channels and transporters are expressed in both the inner ear and kidney. In the inner ear, K(+) cycling and endolymphatic K(+), Na(+), Ca(2+), and pH homeostasis are critical for normal organ function. Ion channels and transporters involved in K(+) cycling include K(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, Na(+)/K(+)-ATPase, Cl(-) channels, connexins, and K(+)/Cl(-) cotransporters. Furthermore, endolymphatic Na(+) and Ca(2+) homeostasis depends on Ca(2+)-ATPase, Ca(2+) channels, Na(+) channels, and a purinergic receptor channel. Endolymphatic pH homeostasis involves H(+)-ATPase and Cl(-)/HCO(3)(-) exchangers including pendrin. Defective connexins (GJB2 and GJB6), pendrin (SLC26A4), K(+) channels (KCNJ10, KCNQ1, KCNE1, and KCNMA1), Na(+)-2Cl(-)-K(+) cotransporter (SLC12A2), K(+)/Cl(-) cotransporters (KCC3 and KCC4), Cl(-) channels (BSND and CLCNKA + CLCNKB), and H(+)-ATPase (ATP6V1B1 and ATPV0A4) cause hearing loss. All these channels and transporters are also expressed in the kidney and support renal tubular transport or signaling. The hearing loss may thus be paralleled by various renal phenotypes including a subtle decrease of proximal Na(+)-coupled transport (KCNE1/KCNQ1), impaired K(+) secretion (KCNMA1), limited HCO(3)(-) elimination (SLC26A4), NaCl wasting (BSND and CLCNKB), renal tubular acidosis (ATP6V1B1, ATPV0A4, and KCC4), or impaired urinary concentration (CLCNKA). Thus, defects of channels and transporters expressed in the kidney and inner ear result in simultaneous dysfunctions of these seemingly unrelated organs.
内耳和肾脏中都表达了多种离子通道和转运体。在内耳中，钾离子循环以及内淋巴中的钾离子、钠离子、钙离子和pH值稳态对于器官的正常功能至关重要。参与钾离子循环的离子通道和转运体包括钾离子通道、钠-2氯-钾共转运体、钠/钾-ATP酶、氯离子通道、连接蛋白和钾/氯共转运体。此外，内淋巴中的钠离子和钙离子稳态依赖于钙-ATP酶、钙通道、钠通道和嘌呤能受体通道。内淋巴的pH值稳态涉及氢-ATP酶和包括pendrin在内的氯/碳酸氢根交换体。连接蛋白（GJB2和GJB6）、pendrin（SLC26A4）、钾离子通道（KCNJ10、KCNQ1、KCNE1和KCNMA1）、钠-2氯-钾共转运体（SLC12A2）、钾/氯共转运体（KCC3和KCC4）、氯离子通道（BSND和CLCNKA + CLCNKB）以及氢-ATP酶（ATP6V1B1和ATPV0A4）的缺陷会导致听力损失。所有这些通道和转运体在肾脏中也有表达，并支持肾小管转运或信号传导。因此，听力损失可能伴有各种肾脏表型，包括近端钠耦联转运的轻微减少（KCNE1/KCNQ1）、钾分泌受损（KCNMA1）、碳酸氢根排泄受限（SLC26A4）、氯化钠流失（BSND和CLCNKB）、肾小管酸中毒（ATP6V1B1、ATPV0A4和KCC4）或尿液浓缩功能受损（CLCNKA）。因此，在肾脏和内耳中表达的通道和转运体缺陷会导致这些看似无关的器官同时出现功能障碍。
