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.
Highlights
The electrochemical balance between intracellular and extracellular compartments is crucial for proper activity of all the tissues and organs
Out of 24 cochleae we examined, in four cochleae, we succeeded in measuring all the electrode located in the endolymph of the scala media, the potential and [K+] in the lateral wall were recorded by doublebarreled microelectrodes sensitive to the [K+] and potential, namely K+-selective microelectrodes
Using the fi-NHK model, here we demonstrated that establishment and a change of the circulation current across the syncytial basolateral surface depend primarily on the Na+ and leak conductances and Na+,K+-ATPases
Summary
The electrochemical balance between intracellular and extracellular compartments is crucial for proper activity of all the tissues and organs. When the activity of syncytial Na+,K+-ATPases was reduced to 46% of their normal value (i.e., blocking rate κOuabain,FC = 0.46), all the simulated steadystate values of EP, vSB, [K+]SY, ISP, and [K+]IS fell approximately within the range of the experimental data obtained during perfusion with 10 μM ouabain (Supplementary Fig. 2a) and resembled their averaged values (Table 1). The dynamics of these solution containing 10 μM ouabain to the perilymphatic space of the scala tympani (Fig. 3d).
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