The unique electrical properties in an extracellular fluid of the mammalian cochlea; their functional roles, homeostatic processes, and pathological significance

Abstract

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.

Evolution of Endolymph Secretion and Endolymphatic Potential Generation in the Vertebrate Inner Ear

“…The Davis theory, elaborated in a series of classical papers between [Davis, 1957, 1961 and still prevailing, asserts that the EP and the hair-cell resting potential, coupled in series, together provide the driving force for the transduction process. Consistent with that, any reduction of the EP, as observed by experimental manipulation or by mutations in the underlying molecular repertoire [Nin et al, 2016], results in hearing impairment. For example, in guinea pigs, a 30 mV drop in the EP entails an approximate 60-dB loss of threshold sensitivity [Manley and Robertson, 1976].…”

“…The mechanisms of its generation by the stria vascularis are known in more detail than for any other vertebrate group [recent reviews in Nin et al, 2016;Fettiplace, 2017;Wangemann and Marcus, 2017] and will be briefly summarized here.…”

Petrosal morphology and cochlear function in Mesozoic stem therians

“…One under-emphasized question that is apparent in the inner ear of all extant 1805 mammals is the conflicting set of demands placed on the auditory hair cells, which are required to alternately transmit and resist transduction currents at unparalleled rates while simultaneously being forced to function at a far remove from the vasculature providing for their nutrition, waste removal and oxygenation [28,62]. While the use of potassium as opposed to sodium is an adaptation for metabolic efficiency seen in the hair cells of all 1810 vertebrates [67,70], the demands for high performance in the therian auditory endorgan seems to place this group's auditory hair cells in a unique metabolic crisis.…”

“…Because monotremes retain the ancestral endolymph-producing capillary plexus in Reissner's membrane (see Fig 13b and f; [16,17]) in 1815 addition to the stria vascularis, and a greater number of radially oriented vessels crossing the cochlear duct [66], they seem to be less liable to metabolic distress than therians. However, the lamentable lack of physiological research on the cochlear apparatus of extant monotremes makes it impossible to judge whether the less specialized anatomy of the cochlear apparatus and supporting vasculature is attributable to weaker cochlear 1820 performance compared to therians, or because of some currently unrecognized requirement for increased cochlear vascularization developed in monotremes [71,62]. The exquisite sensitivity of the stria vascularis and endocochlear potential to induced hypoxia is an immediate and often exploitable feature in physiological studies of modern therians, however [70].…”

“…In particular, this neomorphic drainage may be an evolutionary reaction to the increasing energetic and electrolyte requirements of the enlarging stria vascularis; a structure which in modern therian mammals contains some of the most metabolically active 895 tissues in the body (and contains the only vascularized epithelial tissue known anywhere in mammalian anatomy). As summarized in the discussion section, the stria vascularis is responsible for generating and maintaining the highly positive endolymphatic potential in modern therians [62][63][64]12]. In the extant mammals in which it has been studied it is also an organ with a complex development, recruiting epithelial and connective tissue contributions 900 from cranial ectomesenchyme and other neural crest cell populations [65].…”