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Excitable cochlear hair cells convert the mechanical energy of sounds into the electrical signals necessary for neurotransmission. The key process is cellular depolarization via K+ entry from K+‐enriched endolymph through hair cells' mechanosensitive channels. Positive 80 mV potential in endolymph accelerates the K+ entry, thereby sensitizing hearing. This potential represents positive extracellular potential within the epithelial‐like stria vascularis; the latter potential stems from K+ equilibrium potential (EK) across the strial membrane. Extra‐ and intracellular [K+] determining EK are likely maintained by continuous unidirectional circulation of K+ through a putative K+ transport pathway containing hair cells and stria. Whether and how the non‐excitable tissue stria vascularis responds to acoustic stimuli remains unclear. Therefore, we analysed a cochlear portion for the best frequency, 1 kHz, by theoretical and experimental approaches. We have previously developed a computational model that integrates ion channels and transporters in the stria and hair cells into a circuit and described a circulation current composed of K+. Here, in this model, mimicking of hair cells' K+ flow induced by a 1 kHz sound modulated the circulation current and affected the strial ion transport mechanisms; the latter effect resulted in monotonically decreasing potential and increasing [K+] in the extracellular strial compartment. Similar results were obtained when the stria in acoustically stimulated animals was examined using microelectrodes detecting the potential and [K+]. Measured potential dynamics mirrored the EK change. Collectively, because stria vascularis is electrically coupled to hair cells by the circulation current in vivo too, the strial electrochemical properties respond to sounds. Key points: A highly positive potential of +80 mV in K+‐enriched endolymph in the mammalian cochlea accelerates sound‐induced K+ entry into excitable sensory hair cells, a process that triggers hearing.This unique endolymphatic potential represents an EK‐based battery for a non‐excitable epithelial‐like tissue, the stria vascularis.To examine whether and how the stria vascularis responds to sounds, we used our computational model, in which strial channels and transporters are serially connected to those hair cells in a closed‐loop circuit, and found that mimicking hair cell excitation by acoustic stimuli resulted in increased extracellular [K+] and decreased the battery's potential within the stria.This observation was overall verified by electrophysiological experiments using live guinea pigs.The sensitivity of electrochemical properties of the stria to sounds indicates that this tissue is electrically coupled to hair cells by a radial ionic flow called a circulation current. [ABSTRACT FROM AUTHOR]

The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K to enter sensory hair cells and excite them. The positive EP accelerates this K influx, thereby sensitizing hearing. K exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K to the endolymph. In vivo electrophysiological assays demonstrated that the EP stems primarily from two K diffusion potentials yielded by [K] gradients between intracellular and extracellular compartments in the lateral wall. Such gradients seem to be controlled by ion channels and transporters expressed in particular membrane domains of the two layers. Analyses of human deafness genes and genetically modified mice suggested the contribution of these channels and transporters to EP and hearing. A computational model, which reconstitutes unidirectional K transport by incorporating channels and transporters in the lateral wall and connects this transport to hair cell transcellular K fluxes, simulates the circulation current flowing between the endolymph and the perilymph. In this model, modulation of the circulation current profile accounts for the processes leading to EP loss under pathological conditions. This article not only summarizes the unique physiological and molecular mechanisms underlying homeostasis of the EP and their pathological relevance but also describes the interplay between EP and circulation current. [ABSTRACT FROM AUTHOR]

Abstract: Although salicylate is one of the most widely used nonsteroidal anti-inflammatory drugs, it causes moderate hearing loss and tinnitus at high-dose levels. In the present study, salicylate effects on the K currents in inner hair cells were examined. Salicylate reversibly reduced the outward K currents (I K,f), but did not affect the inward current (I K,n). Salicylate blocked the outward K currents in a concentration-dependent manner according to Hill equation with a half-blocking concentration of 1.66mM, and the Hill coefficient of 1.86. [Copyright &y& Elsevier]