Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol 292: C591-C602, 2007. First published September 27, 2006; doi:10.1152/ajpcell.00560.2005 Free Article
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NERVOUS SYSTEM CELL BIOLOGY

Computational model of vectorial potassium transport by cochlear marginal cells and vestibular dark cells

Imran H. Quraishi and Robert M. Raphael

Department of Bioengineering, Rice University, Houston, Texas

Submitted 1 November 2005 ; accepted in final form 30 August 2006

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.

stria vascularis; endolymph; endocochlear potential; biological modeling


Address for reprint requests and other correspondence: R. M. Raphael, Dept. of Bioengineering, M. S. 142, PO Box 1892, Rice Univ., Houston, TX 77251-1892 (rraphael{at}rice.edu)






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