Computer modeling defines the system driving a constant current crucial for homeostasis in the mammalian cochlea by integrating unique ion transports

Abstract

The 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.