Abstract
AbstractThe cochlear lateral wall—an epithelial-like tissue comprising inner and outer layers—maintains +80 mV in endolymph. This endocochlear potential supports hearing and represents the sum of all membrane potentials across apical and basolateral surfaces of both layers. The apical surfaces are governed by K+ equilibrium potentials. Underlying extracellular and intracellular [K+] is likely controlled by the “circulation current,” which crosses the two layers and unidirectionally flows throughout the cochlea. This idea was conceptually reinforced by our computational model integrating ion channels and transporters; however, contribution of the outer layer’s basolateral surface remains unclear. Recent experiments showed that this basolateral surface transports K+ using Na+, K+-ATPases and an unusual characteristic of greater permeability to Na+ than to other ions. To determine whether and how these machineries are involved in the circulation current, we used an in silico approach. In our updated model, the outer layer’s basolateral surface was provided with only Na+, K+-ATPases, Na+ conductance, and leak conductance. Under normal conditions, the circulation current was assumed to consist of K+ and be driven predominantly by Na+, K+-ATPases. The model replicated the experimentally measured electrochemical properties in all compartments of the lateral wall, and endocochlear potential, under normal conditions and during blocking of Na+, K+-ATPases. Therefore, the circulation current across the outer layer’s basolateral surface depends primarily on the three ion transport mechanisms. During the blockage, the reduced circulation current partially consisted of transiently evoked Na+ flow via the two conductances. This work defines the comprehensive system driving the circulation current.
Publisher
Springer Science and Business Media LLC
Subject
Applied Mathematics,Computer Science Applications,Drug Discovery,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation
Reference55 articles.
1. Von Bekesy, G. Resting potentials inside the cochlear partition of the guinea pig. Nature
169, 241–242 (1952).
2. Smith, C. A., Lowry, O. H. & Wu, M. L. The electrolytes of the labyrinthine fluids. Laryngoscope
64, 141–153 (1954).
3. Hudspeth, A. J. How the ear’s works work. Nature
341, 397–404 (1989).
4. Davis, H. Some principles of sensory receptor action. Physiol. Rev.
41, 391–416 (1961).
5. Ashmore, J. F. & Meech, R. W. Ionic basis of membrane potential in outer hair cells of guinea pig cochlea. Nature
322, 368–371 (1986).
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