{"id":311,"date":"2021-12-30T18:32:46","date_gmt":"2021-12-30T09:32:46","guid":{"rendered":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/?post_type=research-content&p=311"},"modified":"2026-02-26T12:43:26","modified_gmt":"2026-02-26T03:43:26","slug":"cochlea-and-hearing-loss-2","status":"publish","type":"research-content","link":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/research-content\/cochlea-and-hearing-loss-2\/","title":{"rendered":"Cochlea and Hearing Loss"},"content":{"rendered":"\n

\u2777 Biological Battery in the Cochlea<\/strong><\/p>\n\n\n\n

\u3010Outline of the Research Project<\/strong>\u3011<\/strong><\/p>\n\n\n\n

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Figure 1<\/mark> show a cross section of the cochlea, which is made up of three tubular structures. Upper and lower tubules contain \u2018perilymph\u2019, which resembles a regular extracellular solution or blood plasma.  Center tubule is filled with an unusual extracellular solution, \u2018endolymph\u2019, which shows 150 mM [K+<\/sup>] and 2 \u2013 5 mM [Na+<\/sup>]. This profile looks like the properties in an intracellular solution. In addition, the endolymph always exhibits a highly positive potential<\/strong> of +80 \u2013 +100 mV with reference to the perilymph. These unique electrochemical properties are essential for high sensitivity observed in mammalian hearing. In particular, the high potential is a key; its disruption results in deafness.<\/span><\/p>\n<\/div>\n\n\n\n

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Figure 1<\/span>\u3000A cross section of the cochlea and stria vascularis<\/figcaption><\/figure><\/div>\n<\/div>\n<\/div>\n\n\n\n
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The milieu of the endolymph has been considered to be maintained by K+<\/sup>-circulation<\/strong> or K+<\/sup>-recycling between this fluid and the perilymph. This unidirectional ion transport is likely to be driven by \u2018stria vascularis\u2019<\/strong>, an epithelial-like tissue composed of inner and outer layers.<\/span><\/mark> However, it has remained uncertain how the K+<\/sup>-circulation actually contributes to the endolymph in vivo<\/em>.<\/p>\n<\/div>\n\n\n\n

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Figure 2<\/span>\u3000Ion transport mechanisms in the stria vascularis<\/figcaption><\/figure>\n<\/div>\n<\/div>\n\n\n\n

We have focused on the high potential of the endolymph and addressed the mechanism underlying this electrical element on the basis of the results described by our and other groups, as follows. Firstly, the K+<\/sup>-circulation depends on functional coupling of ion channels and transporters in the stria vascularis (Fig. 2<\/span>). Secondly, the origin of the endolymphatic potential is strial two batteries, which are connected in series are controlled by the K+<\/sup>-circulation. Thirdly, these two issues are integrated and linked with hair-cell\u2019s activity in vivo<\/em>, resulting in maintenance of the endolymphatic potential [refs: 5-12]. In this context, acoustic stimuli, which excite hair cells, induce the K+<\/sup>-circulation and thereby affected the batteries [ref: 1]. Moreover, interference with a crucial factor involved in the K+<\/sup>-circulation by optogenetic approach caused repetitive acute hearing loss observed in clinical sites [ref: 4].<\/p>\n\n\n\n

\u3010Experimental Procedures<\/strong>\u3011<\/p>\n\n\n\n

Go to the page entitled ‘Analytical instruments<\/span><\/a>\u2019<\/em> to see the details.<\/p>\n\n\n\n

(1) Molecular biological and histological methods<\/a><\/span><\/span> [refs: 4, 5, 13]
These methods are used to identify the molecular basis and tissue and cellular localization of the ion channels and transporters involved in driving the K+<\/sup>-circulation.<\/p>\n\n\n\n

(2)<\/span> Comprehensive analysis of the proteins<\/span> [refs: 2, 14]
With comprehensive approaches using HPLC and LC-MS\/MS, we are working on clarification of the profile of the proteins that contribute to the K+<\/sup>-circulation.  This project is carried out by collaborating with Profs. Yoshikatsu Kanai<\/span> and Shuji Nagamori<\/span>.<\/p>\n\n\n\n

(3) Ion selective microelectrodes<\/a><\/span><\/span> [refs: 5-11]
The K+<\/sup>-circulation maintains the high potential in the endolymph by regulating [K+<\/sup>] in the lateral wall.  Therefore, it is crucial for the project to examine the dynamics of K+<\/sup> profile. We fabricate ion selective microelectrode that monitor the potential and [K+<\/sup>] in the microenvironment \u2018simultaneously and in real time\u2019 and use this sensor for in vivo<\/em> measurements.<\/p>\n\n\n\n

(4) Computer simulation<\/a><\/span><\/span> [refs: 1, 5, 10]
Some of vital phenomena cannot be measured by any experimental techniques. Indeed, in this project, we are unable to directly detect ionic flows through the channels or transporters in vivo<\/em>. This issue is accessible by means of theoretical approaches. We have constructed a number of equations that represent the ion channels and transporters in the stria vascularis and integrated these ionic flows to those in sensory hair cells in silico<\/em>. This \u2018Nin-Hibino-Kurachi (NHK) model\u2019<\/strong> can reconstitute the K+<\/sup>-circulation as well as the electrochemical properties of the stria and endolymph in different conditions [ref: 10]. This model has recently renewed with the experimental observations (fi-NHK model<\/strong>) (for source code, see <\/span>the linkpage<\/span>)<\/a> [5]. With this updated version, we showed the response of the stria vascularis when the hair cells are stimulated by sounds. We will further improve the model via feedback from the experimental results and use for a variety of projects in the future.<\/p>\n\n\n\n

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Overview: How Does The Cochlea
of the Inner Ear Work?<\/strong><\/a><\/div>\n<\/div>\n<\/div>\n\n\n\n
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\u3000Project \u2776\uff1a <\/strong>
Nanoscale Vibrations in Cochlear Sensory Epithelium<\/strong><\/strong>\u3000<\/a><\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"featured_media":0,"template":"","research-content_cat":[16],"class_list":["post-311","research-content","type-research-content","status-publish","hentry","research-content_cat-rc-main2-child"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/wp-json\/wp\/v2\/research-content\/311","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/wp-json\/wp\/v2\/research-content"}],"about":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/wp-json\/wp\/v2\/types\/research-content"}],"wp:attachment":[{"href":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/wp-json\/wp\/v2\/media?parent=311"}],"wp:term":[{"taxonomy":"research-content_cat","embeddable":true,"href":"https:\/\/www.med.osaka-u.ac.jp\/pub\/pharma2\/english\/wp-json\/wp\/v2\/research-content_cat?post=311"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}