Expression of voltage-gated potassium channels in the inner ear and herediatary deafness : molecular biological analysis

1.抑制整流钾通道Kir4.1在耳蜗血管纹、耳蜗支持细胞和螺旋神经节细胞周围的卫星细胞表达。Kir4.1也见于外沟细胞。提示外沟细胞内向整流性Kir4.1钾通道可能在钾离子通过缝隙连接的循环机制中起重要作用。2. Brn-4缺失时，耳蜗外侧壁II型纤维细胞Na，K-ATP酶样免疫反应性明显降低。连接蛋白26在突变耳蜗外侧壁的纤维细胞中稀疏分布。与此相反，Na，K-ATP酶和电压门控钾通道KCNQ 1在血管纹的边缘细胞在这个突变体中大量表达。这些结果提示，人DFN 3非综合征性耳聋耳蜗外侧壁纤维细胞功能障碍和缝隙连接的K+循环通路中断可能导致耳蜗内电位降低和严重听力损失。3.在螺旋韧带的I型纤维细胞、II型纤维细胞和耳蜗上纤维细胞中发现了强烈的GLAST样免疫反应。谷氨酰胺合成酶在螺旋韧带的I型纤维细胞、II型纤维细胞、III型纤维细胞和腹上纤维细胞、血管纹的基底细胞中大量表达。这些结果表明，丰富的GLAST和谷氨酰胺合成酶的结缔组织细胞在耳蜗可能的功能，以维持外淋巴谷氨酸浓度在一个低的（无毒）水平。

1.Inwardly rectifying potassium channel Kir4.1 was expressed in the stria vascularis, cochlear supporting cell and satellite cells surround spiral ganglion cells. Kir4.1 was also found in the outer sulcus cells. These results suggest that inwardly rectifying Kir4.1 potassium channel in the outer sulcus cells may play a important role in the potassium ion recycling mechanism via gap junctions.2.In the Brn-4-deficient, Na, K-ATPase-like immunoreactivity in the type II fibrocytes of the cochlear lateral wall was remarkably decreased. Connexin 26 was sparsely distributed among the fibrocytes in the mutant cochlear lateral wall. In contrast, Na, K-ATPase and voltage-gated potassium channel KCNQ1 were abundantly expressed in the marginal cells of the stria vascularis in this mutant. These findings suggest that a dysfunction of fibrocytes in the cochlear lateral wall and an interruption of the K+ ion recycling pathway via gap junctions may result in the depression of endocochlear potential and profound hearing loss in human DFN3 non-syndromic deafness.3.Intense GLAST-like immunoreactivity was found in the type I fibocytes, type II fibrocytes and the suprastrial fibrocytes in the spiral ligament. Glutamine synthetase was abundantly expressed in the type I fibrocytes, the type II fibrocytes, the type III fibrocytes and the suprastrial fibrocytes in the spiral ligament, the basal cells of the stria vascularis. These results suggest that abundant GLAST and glutamine synthetase in the connective tissue cells in the cochlea may function to maintain the perilymphatic glutamate concentration at a low (nontoxic) level.