Cochlear marginal cells and vestibular dark cells transport potassium into the inner ear endolymph, a potassium-rich fluid, the homeostasis of which is essential for hearing and balance. We have formulated an integrated mathematical model of ion transport across these epithelia that incorporates the biophysical properties of the major ion transporters and channels located in the apical and basolateral membranes of the constituent cells. The model is constructed for both open- and short-circuit situations to test the extremes of functional capacity of the epithelium and predicts the steady-state voltages, ion concentrations, and transepithelial currents as a function of various transporter and channel densities. We validate the model by establishing that the cells are capable of vectorial ion transport consistent with several experimental measurements. The model indicates that cochlear marginal cells do not make a significant direct contribution to the endocochlear potential and illustrates how changes to the activity of specific transport proteins lead to reduced K(+) flux across the marginal and dark cell layers. In particular, we investigate the mechanisms of loop diuretic ototoxicity and diseases with hearing loss in which K(+) and Cl(-) transport are compromised, such as Jervell and Lange-Nielsen syndrome and Bartter syndrome, type IV, respectively. Such simulations demonstrate the utility of compartmental modeling in investigating the role of ion homeostasis in inner ear physiology and pathology.

译文

:耳蜗边缘细胞和前庭暗细胞将钾转运到内耳内淋巴,这是一种富含钾的液体,其稳态对听力和平衡至关重要。我们已经制定了一个跨这些上皮细胞的离子迁移的综合数学模型,该模型整合了主要离子转运蛋白和位于组成细胞顶膜和基底外侧膜中的通道的生物物理特性。该模型适用于开路和短路情况,以测试上皮的功能极限,并预测稳态电压,离子浓度和跨上皮电流随各种转运蛋白和通道密度的变化。我们通过建立细胞能够进行矢量离子运输与几个实验测量结果一致的方法来验证模型。该模型表明,耳蜗边缘细胞对内耳蜗电位没有显着直接贡献,并说明了特定转运蛋白活性的变化如何导致跨边缘和黑暗细胞层的K()通量降低。特别是,我们研究了of利尿剂的耳毒性和机制,其中K()和Cl(-)的运输受到损害的听力损失的疾病,例如分别为IV型Jervell和Lange-Nielsen综合征和Bartter综合征。这样的模拟证明了隔室模型在研究离子稳态在内耳生理和病理中的作用方面的实用性。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录