Higashiyama Kasumi, Takeuchi Shunji, Azuma Hiroshi, Sawada Shoichi, Kakigi Akinobu, Takeda Taizo
Department of Otolaryngology, Kochi Medical School, Kochi, Japan.
ORL J Otorhinolaryngol Relat Spec. 2010;71 Suppl 1:57-66. doi: 10.1159/000265125. Epub 2010 Feb 24.
In the stria vascularis (SV), it is known that the Na(+)-K(+)-ATPase is expressed abundantly and its activity in the basolateral membrane of marginal cells is high. Ouabain, an inhibitor of the Na(+)-K(+)-ATPase, causes not only a decline in the endocochlear DC potential but also acute vacuolar formation in marginal cells. We studied the ionic mechanisms underlying the ouabain-induced vacuolar formation in marginal cells using perilymphatic perfusion in guinea pigs. Perilymphatic perfusion with 1 mM ouabain dissolved in the artificial perilymph for 50 min caused many vacuoles of a wide range of sizes in the apical cytoplasm of marginal cells, the bulging of marginal cells into the scala media and strial volume increase. Removal of K(+) from the perilymph reduced the proportion of vacuoles and strial thickening, but the bulging of marginal cells remained. In contrast, the sizes of vacuoles were drastically reduced and extrusion of marginal cells into the scala media could not be observed in the absence of perilymphatic Na(+). Furthermore, the total volume of SV was obviously reduced in comparison with the control. These results indicate that perilymphatic Na(+) and K(+) are responsible for these morphological changes caused by ouabain, and that perilymphatic Na(+) plays an important role in the cellular volume regulation in SV in the presence of ouabain. It is supposed that the transport system of perilymphatic Na(+) and K(+) into marginal cells may contribute to vacuolar formation when ouabain is administered. Regarding Na(+), we hypothesize two possibilities for the perilymphatic Na(+) transporting pathway as follows. Na(+) in the perilymph could enter the endolymph via Reissner's membrane or the basilar membrane; Na(+) in the endolymph would then be taken up by marginal cells via the apical membrane and secreted into the intrastrial space by Na(+)-K(+)-ATPase in the basolateral membrane. Another, less likely, possibility is that Na(+) in the perilymph is transported into basal cells or fibrocytes in the spiral ligament, then into intermediate cells via gap junctions, and finally secreted into the intrastrial space via Na(+)-K(+)-ATPase of intermediate cells. Regarding K(+), it is expected that the K(+) recycling pathway plays a role in ouabain-induced vacuolar formation in marginal cells.
在血管纹（SV）中，已知钠钾ATP酶大量表达，其在边缘细胞基底外侧膜中的活性很高。哇巴因是钠钾ATP酶的抑制剂，它不仅会导致内淋巴直流电位下降，还会使边缘细胞急性空泡形成。我们利用豚鼠的外淋巴灌注研究了哇巴因诱导边缘细胞空泡形成的离子机制。用溶解在人工外淋巴中的1 mM哇巴因进行外淋巴灌注50分钟，会导致边缘细胞顶端细胞质中出现许多大小各异的空泡，边缘细胞向中阶突出，血管纹体积增大。从外淋巴中去除钾会减少空泡比例和血管纹增厚，但边缘细胞的突出仍会存在。相反，在没有外淋巴钠的情况下，空泡大小会急剧减小，且无法观察到边缘细胞向中阶的挤出。此外，与对照组相比，血管纹的总体积明显减小。这些结果表明，外淋巴中的钠和钾是哇巴因引起这些形态变化的原因，并且在外淋巴存在哇巴因的情况下，外淋巴钠在血管纹细胞体积调节中起重要作用。据推测，当给予哇巴因时，外淋巴钠和钾进入边缘细胞的转运系统可能有助于空泡形成。关于钠，我们假设外淋巴钠转运途径有两种可能性，如下所述。外淋巴中的钠可通过Reissner膜或基底膜进入内淋巴；内淋巴中的钠随后会通过顶端膜被边缘细胞摄取，并通过基底外侧膜中的钠钾ATP酶分泌到血管纹间隙。另一种可能性较小的情况是，外淋巴中的钠被转运到螺旋韧带中的基底细胞或纤维细胞中，然后通过缝隙连接进入中间细胞，最后通过中间细胞的钠钾ATP酶分泌到血管纹间隙。关于钾，预计钾循环途径在哇巴因诱导的边缘细胞空泡形成中起作用。
