KCNJ10 (Kir4.1) potassium channel knockout abolishes endocochlear potential

2002 ◽  
Vol 282 (2) ◽  
pp. C403-C407 ◽  
Author(s):  
Daniel C. Marcus ◽  
Tao Wu ◽  
Philine Wangemann ◽  
Paulo Kofuji
Keyword(s):  
Driving Force ◽  
Stria Vascularis ◽  
Endocochlear Potential ◽  
Sensory Transduction ◽  
Basal Cells ◽  
Transport Pathways ◽  
Main Charge ◽  
Marginal Cells ◽  
Intermediate Cells ◽  
Two Barriers

Stria vascularis of the cochlea generates the endocochlear potential and secretes K+. K+ is the main charge carrier and the endocochlear potential the main driving force for the sensory transduction that leads to hearing. Stria vascularis consists of two barriers, marginal cells that secrete potassium and basal cells that are coupled via gap junctions to intermediate cells. Mice lacking the KCNJ10 (Kir4.1) K+ channel in strial intermediate cells did not generate an endocochlear potential. Endolymph volume and K+ concentration ([K+]) were reduced. These studies establish that the KCNJ10 K+ channel provides the molecular mechanism for generation of the endocochlear potential in concert with other transport pathways that establish the [K+] difference across the channel. KCNJ10 is also a limiting pathway for K+ secretion.

Another role for melanocytes: their importance for normal stria vascularis development in the mammalian inner ear

Development ◽  
1989 ◽  
Vol 107 (3) ◽  
pp. 453-463 ◽  
Author(s):  
K.P. Steel ◽  
C. Barkway
Keyword(s):  
Neural Crest ◽  
Basal Cell ◽  
Stria Vascularis ◽  
Normal Adult ◽  
Basal Cells ◽  
Cochlear Duct ◽  
Cell Layers ◽  
Marginal Cells ◽  
Intermediate Cells ◽  
And Function

The stria vascularis of the mammalian cochlea is composed primarily of three types of cells. Marginal cells line the lumen of the cochlear duct and are of epithelial origin. Basal cells also form a continuous layer and they may be mesodermal or derived from the neural crest. Intermediate cells are melanocyte-like cells, presumably derived from the neural crest, and are scattered between the marginal and basal cell layers. The marginal cells form extensive interdigitations with the basal and intermediate cells in the normal adult stria. The stria also contains a rich supply of blood vessels. We investigated the role of melanocytes in the stria vascularis by studying its development in a mouse mutant, viable dominant spotting, which is known to have a primary neural crest defect leading to an absence of recognisable melanocytes in the skin. Melanocytes were not found in the stria of most of the mutants examined, and from about 6 days of age onwards a reduced amount of interdigitation amongst the cells of the stria was observed. These ultrastructural anomalies were associated with strial dysfunction. In the normal adult mammal, the stria produces an endocochlear potential (EP), a resting dc potential in the endolymph in the cochlear duct, which in mice is normally about +100 mV. In our control mice, EP rose to adult levels between 6 and 16 days after birth. In most of the mutants we studied, EP was close to zero at all ages from 6 to 20 days. Melanocyte-like cells appear to be vital for normal stria vascularis development and function. They may be necessary to facilitate the normal process of interdigitation between marginal and basal cell processes at a particular stage during development, and the lack of adequate interdigitation in the mutants may be the cause of their strial dysfunction. Alternatively, melanocytes may have some direct, essential role in the production of an EP by the stria. Melanocytes may be important both for normal strial development and for the production of the EP. We believe this is the clearest demonstration yet of a role for migratory melanocytes other than their role in pigmentation.

Positive endocochlear potential: Mechanism of production by marginal cells of stria vascularis

1987 ◽  
Vol 29 (2-3) ◽  
pp. 117-124 ◽  
Author(s):  
Franklin F. Offner ◽  
Peter Dallos ◽  
Mary Ann Cheatham
Keyword(s):  
Stria Vascularis ◽  
Endocochlear Potential ◽  
Potential Mechanism ◽  
Marginal Cells

Horseradish Peroxidase Permeation from the Capillaries of the Stria Vascularis after Inoculation of Endotoxin into the Middle Ear

1997 ◽  
Vol 106 (5) ◽  
pp. 394-398 ◽  
Author(s):  
Kensuke Watanabe ◽  
Yasuo Tanaka
Keyword(s):  
Horseradish Peroxidase ◽  
Middle Ear ◽  
Stria Vascularis ◽  
Femoral Vein ◽  
Cell Junctions ◽  
Intercellular Spaces ◽  
Basal Turn ◽  
Pinocytotic Vesicles ◽  
Marginal Cells ◽  
Intermediate Cells

Escherichia coli-derived endotoxin was inoculated in the middle ear of guinea pigs 24 hours after being injected intraperitoneally. Twenty-four hours after the middle ear inoculation, horseradish peroxidase (HRP) was injected via the femoral vein and the permeability of HRP through the capillaries of the stria vascularis and the destination of the leaked HRP were examined. A large amount of HRP leaked out of the capillary through the opened endothelial cell junctions and penetrated the enlarged intercellular spaces. Leaked HRP entered the pinocytotic vesicles of the intermediate cells. Even slightly degenerated intermediate cells retained this function. The HRP penetrated the spongelike structure of the marginal cells leading to the intercellular space. This structure was not observed without endotoxin. The HRP could not pass to the cochlear duct through the tight junctions between marginal cells. Blood sludging was observed in the strial capillaries. It appeared more frequently in the upper three turns than in the basal turn. The HRP leakage out of the capillaries was observed not only in the upper three turns but also in the basal turn.

Gastric type H+,K+-ATPase in the cochlear lateral wall is critically involved in formation of the endocochlear potential

2006 ◽  
Vol 291 (5) ◽  
pp. C1038-C1048 ◽  
Author(s):  
Toshiaki Shibata ◽  
Hiroshi Hibino ◽  
Katsumi Doi ◽  
Toshihiro Suzuki ◽  
Yasuo Hisa ◽  
...  
Keyword(s):  
Stria Vascularis ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Lateral Wall ◽  
Endocochlear Potential ◽  
Pcr Analysis ◽  
Spiral Ligament ◽  
Gastric Type ◽  
Marginal Cells ◽  
Strong Immunoreactivity

Cochlear endolymph has a highly positive potential of approximately +80 mV known as the endocochlear potential (EP). The EP is essential for hearing and is maintained by K+ circulation from perilymph to endolymph through the cochlear lateral wall. Various K+ transport apparatuses such as the Na+,K+-ATPase, the Na+-K+-2Cl− cotransporter, and the K+ channels Kir4.1 and KCNQ1/KCNE1 are expressed in the lateral wall and are known to play indispensable roles in cochlear K+ circulation. The gastric type of the H+,K+-ATPase was also shown to be expressed in the cochlear lateral wall (Lecain E, Robert JC, Thomas A, and Tran Ba Huy P. Hear Res 149: 147–154, 2000), but its functional role has not been well studied. In this study we examined the precise localization of H+,K+-ATPase in the cochlea and its involvement in formation of EP. RT-PCR analysis showed that the cochlea expressed mRNAs of gastric α1-, but not colonic α2-, and β-subunits of H+,K+-ATPase. Immunolabeling of an antibody specific to the α1 subunit was detected in type II, IV, and V fibrocytes distributed in the spiral ligament of the lateral wall and in the spiral limbus. Strong immunoreactivity was also found in the stria vascularis. Immunoelectron microscopic examination exhibited that the H+,K+-ATPase was localized exclusively at the basolateral site of strial marginal cells. Application of Sch-28080, a specific inhibitor of gastric H+,K+-ATPase, to the spiral ligament as well as to the stria vascularis caused prominent reduction of EP. These results may imply that the H+,K+-ATPase in the cochlear lateral wall is crucial for K+ circulation and thus plays a critical role in generation of EP.

MRL/MP-lpr/lpr Mouse as a Model of Immune-Induced Sensorineural Hearing Loss

1992 ◽  
Vol 101 (10_suppl) ◽  
pp. 82-86 ◽  
Author(s):  
Chikashi Kusakari ◽  
Koji Hozawa ◽  
Masahisa Kyogoku ◽  
Shuji Koike ◽  
Tomonori Takasaka
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Stria Vascularis ◽  
Sensorineural Hearing ◽  
Response Threshold ◽  
Auditory Brain Stem Response ◽  
Auditory Brain Stem ◽  
Hearing Acuity ◽  
Marginal Cells ◽  
Intermediate Cells

Hearing acuity and inner ear disorders of MRL/ lpr mice, bred for the study of autoimmune disease, were examined in comparison to those of BALB/c mice. The auditory brain stem response threshold of 20-week-old MRL/ lpr mice was significantly higher than that of BALB/c mice of the same age (p < .01). The pathologic changes of 20-week-old MRL/ lpr mice were characterized by the degeneration of intermediate cells, widened intercellular spaces, and immunoglobulin G deposition on the basement membrane of strial blood vessels as well as in the basal infolding of strial marginal cells, which were absent in BALB/c mice. That there were no other evident pathologic findings in the cochlea or middle ear suggests that these changes in the stria vascularis seemed to be responsible for the sensorineural hearing loss of this mouse. The MRL/ lpr mouse was thought to be a good experimental model to study the spontaneous sensorineural hearing loss caused by an immune reaction.

Distribution and significance of endothelin 1 in guinea pig cochlear lateral wall

2007 ◽  
Vol 121 (8) ◽  
pp. 721-724 ◽  
Author(s):  
D-Y Xu ◽  
Y-D Tang ◽  
S-X Liu ◽  
J Liu
Keyword(s):  
Guinea Pig ◽  
Stria Vascularis ◽  
Lateral Wall ◽  
Complex Method ◽  
Spiral Ligament ◽  
Basal Cells ◽  
Endothelin 1 ◽  
Marginal Cells ◽  
Spiral Ligament Fibrocytes ◽  
Avidin Biotin Complex

AbstractEndothelin 1 is a vasoconstrictive peptide with many biological functions. To investigate the distribution of endothelin 1 in guinea pig cochlear lateral wall and the significance of endothelin 1 in maintaining cochlear homeostasis, the immunohistochemistry avidin biotin complex method was applied by using rabbit anti-endothelin 1 polyclonal antibody as primary antibody. Endothelin-1-like activities were detected in the marginal cells, spiral prominence epithelial cells, outer sulcus cells, stria vascularis capillaries, basal cells and spiral ligament fibrocytes.These results suggest that endothelin 1 may play an important role in maintaining cochlear homeostasis.

scholarly journals Loss of cochlear HCO3− secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model

2007 ◽  
Vol 292 (5) ◽  
pp. F1345-F1353 ◽  
Author(s):  
Philine Wangemann ◽  
Kazuhiro Nakaya ◽  
Tao Wu ◽  
Rajanikanth J. Maganti ◽  
Erin M. Itza ◽  
...  
Keyword(s):  
Hair Cells ◽  
Anion Exchanger ◽  
Stria Vascularis ◽  
Endocochlear Potential ◽  
Sensory Transduction ◽  
Pendred Syndrome ◽  
Cell Degeneration ◽  
Childhood Deafness ◽  
Auditory Brain Stem ◽  
Sensory Hair Cells

Pendred syndrome, characterized by childhood deafness and postpuberty goiter, is caused by mutations of SLC26A4, which codes for the anion exchanger pendrin. The goal of the present study was to determine how loss of pendrin leads to hair cell degeneration and deafness. We evaluated pendrin function by ratiometric microfluorometry, hearing by auditory brain stem recordings, and expression of K+ and Ca2+ channels by confocal immunohistochemistry. Cochlear pH and Ca2+ concentrations and endocochlear potential (EP) were measured with double-barreled ion-selective microelectrodes. Pendrin in the cochlea was characterized as a formate-permeable and DIDS-sensitive anion exchanger that is likely to mediate HCO3− secretion into endolymph. Hence endolymph in Slc26a4+/− mice was more alkaline than perilymph, and the loss of pendrin in Slc26a4−/− mice led to an acidification of endolymph. The stria vascularis of Slc26a4−/− mice expressed the K+ channel Kcnj10 and generated a small endocochlear potential before the normal onset of hearing at postnatal day 12. This small potential and the expression of Kcnj10 were lost during further development, and Slc26a4−/− mice did not acquire hearing. Endolymphatic acidification may be responsible for inhibition of Ca2+ reabsorption from endolymph via the acid-sensitive epithelial Ca2+ channels Trpv5 and Trpv6. Hence the endolymphatic Ca2+ concentration was found elevated in Slc26a4−/− mice. This elevation may inhibit sensory transduction necessary for hearing and promote the degeneration of the sensory hair cells. Degeneration of the hair cells closes a window of opportunity to restore the normal development of hearing in Slc26a4−/− mice and possibly human patients suffering from Pendred syndrome.

scholarly journals Preferential Cochleotoxicity of Cisplatin

2021 ◽  
Vol 15 ◽  
Author(s):  
Pattarawadee Prayuenyong ◽  
David M. Baguley ◽  
Corné J. Kros ◽  
Peter S. Steyger
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Driving Force ◽  
Stria Vascularis ◽  
Endocochlear Potential ◽  
Current Evidence ◽  
Cochlear Hair Cells ◽  
Anatomy And Physiology ◽  
Mechanoelectrical Transduction ◽  
Direct Exposure

Cisplatin-induced ototoxicity in humans is more predominant in the cochlea than in the vestibule. Neither definite nor substantial vestibular dysfunction after cisplatin treatment has been consistently reported in the current literature. Inner ear hair cells seem to have intrinsic characteristics that make them susceptible to direct exposure to cisplatin. The existing literature suggests, however, that cisplatin might have different patterns of drug trafficking across the blood-labyrinth-barrier, or different degrees of cisplatin uptake to the hair cells in the cochlear and vestibular compartments. This review proposes an explanation for the preferential cochleotoxicity of cisplatin based on current evidence as well as the anatomy and physiology of the inner ear. The endocochlear potential, generated by the stria vascularis, acting as the driving force for hair cell mechanoelectrical transduction might also augment cisplatin entry into cochlear hair cells. Better understanding of the stria vascularis might shed new light on cochleotoxic mechanisms and inform the development of otoprotective interventions to moderate cisplatin associated ototoxicity.

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