Vestibular hair bundles control pH with (Na+, K+)/H+ exchangers NHE6 and NHE9
Vestibular hair bundles control pH with (Na+, K+)/H+ exchangers NHE6 and NHE9
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DOI：
10.1523/jneurosci.2990-06.2006
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发表时间：
2006-09-27
影响因子：
5.3
通讯作者：
Gillespie, Peter G.
中科院分区：
文献类型：
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作者：
Hill, Jennifer K.;Brett, Christopher L.;Gillespie, Peter G.
在内耳毛细胞中，质膜Ca（2+）-ATP酶介导的强Ca（2+）/H（+）交换会迅速酸化机械敏感的毛束，而没有有效去除H（+）。我们发现，蛙球囊前庭毛细胞的基底外侧膜通过Na（+）依赖性机制排出H（+），而在缺乏Na（+）和HCO 3（-）的情况下，即使索马体被酸化，束也能迅速清除H（+）。K（+）完全有效且足以去除H（+）;相反，Rb（+）未能支持pH恢复。Na（+）/ H（+）-交换体亚型1（NHE 1）存在于毛细胞索马膜上，可能负责Na（+）依赖性H（+）排出。NHE 6和NHE 9是细胞器同种型，可以瞬时出现在质膜上，并已被提出介导K（+）/ H（+）交换。我们发现NHE 6在一个子集的毛束，NHE 9是目前在所有束。在缺乏内源性交换剂的酵母菌株中，这些异构体的异源表达赋予了对高水平KCl和NaCl的pH依赖性耐受性。NHE 9优选的阳离子的顺序为K（+）、Na（+）>> Rb（+），这与这些离子在促进毛束中pH恢复中的相对功效一致。电中性K（+）/ H（+）交换，我们建议由NHE 9在毛束中进行，利用高K（+）内淋巴，仅对跨束膜的pH不平衡做出反应，不受+80 mV耳蜗内电位的影响，并使用耳中已经存在的K（+）再循环机制。这种机制允许毛细胞去除由Ca（2+）泵送产生的H（+），而细胞中没有ATP水解。
In hair cells of the inner ear, robust Ca (2+)/H (+) exchange mediated by plasma-membrane Ca (2+) -ATPase would rapidly acidify mechanically sensitive hair bundles without efficient removal of H (+). We found that, whereas the basolateral membrane of vestibular hair cells from the frog saccule extrudes H (+) via an Na (+)-dependent mechanism, bundles rapidly remove H (+) in the absence of Na (+) and HCO3 (-), even when the soma is acidified. K (+) was fully effective and sufficient for H (+) removal; in contrast, Rb (+) failed to support pH recovery. Na (+)/ H (+) -exchanger isoform 1 (NHE1) was present on hair-cell soma membranes and was likely responsible for Na (+) -dependent H (+) extrusion. NHE6 and NHE9 are organellar isoforms that can appear transiently on plasma membranes and have been proposed to mediate K (+)/ H (+) exchange. We identified NHE6 in a subset of hair bundles; NHE9 was present in all bundles. Heterologous expression of these isoforms in yeast strains lacking endogenous exchangers conferred pH-dependent tolerance to high levels of KCl and NaCl. NHE9 preferred cations in the order K (+), Na (+) >> Rb (+) consistent with the relative efficacies of these ions in promoting pH recovery in hair bundles. Electroneutral K (+)/ H (+) exchange, which we propose is performed by NHE9 in hair bundles, exploits the high-K (+) endolymph, responds only to pH imbalance across the bundle membrane, is unaffected by the + 80mV endocochlear potential, and uses mechanisms already present in the ear for K (+) recycling. This mechanism allows the hair cell to remove H (+) generated by Ca (2+) pumping without ATP hydrolysis in the cell.