Computational model of vectorial potassium transport by cochlear marginal cells and vestibular dark cells
Computational model of vectorial potassium transport by cochlear marginal cells and vestibular dark cells
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DOI：
10.1152/ajpcell.00560.2005
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发表时间：
2007-01-01
影响因子：
5.5
通讯作者：
Raphael, Robert M.
中科院分区：
文献类型：
--
作者：
Quraishi, Imran H.;Raphael, Robert M.
耳蜗边缘细胞和前庭暗细胞将钾转运到内耳内淋巴中，内耳内淋巴是一种富含钾的液体，其体内平衡对听力和平衡至关重要。我们已经制定了一个集成的数学模型，离子转运这些上皮细胞，结合了生物物理特性的主要离子转运蛋白和通道位于顶端和基底侧膜的组成细胞。该模型被构建为开路和短路的情况下，测试的极端功能的上皮细胞的能力，并预测的稳态电压，离子浓度，和跨上皮电流作为各种转运蛋白和通道密度的函数。我们通过建立细胞能够与几个实验测量相一致的矢量离子传输来验证该模型。该模型表明，耳蜗边缘细胞不作出显着的直接贡献的耳蜗内电位，并说明如何改变特定的转运蛋白的活性导致减少K+通量的边缘和暗细胞层。特别是，我们研究了耳袢利尿剂耳毒性和听力损失疾病的机制，其中K+和Cl-转运受损，如Jervell和Lange-Nielsen综合征和Bartter综合征，IV型，分别。这样的模拟证明了房室模型在研究离子稳态在内耳生理学和病理学中的作用中的实用性。
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.