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1.
Hear Res ; 330(Pt A): 90-7, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26119178

ABSTRACT

Kölliker's organ is a transient epithelial structure, comprising a major part of the organ of Corti during pre-hearing stages of development. The auditory system is spontaneously active during development, which serves to retain and refine neural connections. Kölliker's organ is considered a key candidate for generating such spontaneous activity, most likely through purinergic (P2 receptor) signalling and inner hair cell (IHC) activation. Associated with the spontaneous neural activity, ATP released locally by epithelial cells induces rhythmic morphological changes within Kölliker's organ, the purpose of which is not understood. These changes are accompanied by a shift in cellular refractive index, allowing optical detection of this activity in real-time. Using this principle, we investigated the origin of spontaneous morphological activity within Kölliker's organ. Apical turns of Wistar rat cochleae (P9-11) were dissected, and the purinergic involvement was studied following acute tissue exposure to a P2 receptor agonist (ATPγS) and antagonist (suramin). ATPγS induced a sustained darkening throughout Kölliker's organ, reversed by suramin. This effect was most pronounced in the region closest to the inner hair cells, which also displayed the highest frequency of intrinsic morphological events. Additionally, suramin alone induced swelling of this region, suggesting a tight regulation of cell volume by ATP-mediated mechanisms. Histological analysis of cochlear tissues demonstrates the most profound volume changes in the border cell region immediately adjacent to the IHCs. Together, these results underline the role of purinergic signalling in initiating morphological events within Kölliker's organ, and suggest a key involvement of border cells surrounding IHCs in regulating this spontaneous activity.


Subject(s)
Gap Junctions/metabolism , Organ of Corti/growth & development , Organ of Corti/physiology , Adenosine Triphosphate/analogs & derivatives , Adenosine Triphosphate/chemistry , Adenosine Triphosphate/metabolism , Animals , Cochlea/metabolism , Epithelial Cells/metabolism , Female , Hair Cells, Auditory/cytology , Hair Cells, Auditory, Inner/drug effects , Hearing/physiology , Hydrolysis , Image Processing, Computer-Assisted , Immunohistochemistry , Male , Organ of Corti/cytology , Rats , Rats, Wistar , Receptors, Purinergic/metabolism , Signal Transduction , Suramin/therapeutic use
2.
Biomed Res Int ; 2014: 367939, 2014.
Article in English | MEDLINE | ID: mdl-25210710

ABSTRACT

Prior to the "onset of hearing," developing cochlear inner hair cells (IHCs) and primary auditory neurons undergo experience-independent activity, which is thought to be important in retaining and refining neural connections in the absence of sound. One of the major hypotheses regarding the origin of such activity involves a group of columnar epithelial supporting cells forming Kölliker's organ, which is only present during this critical period of auditory development. There is strong evidence for a purinergic signalling mechanism underlying such activity. ATP released through connexin hemichannels may activate P2 purinergic receptors in both Kölliker's organ and the adjacent IHCs, leading to generation of electrical activity throughout the auditory system. However, recent work has suggested an alternative origin, by demonstrating the ability of IHCs to generate this spontaneous activity without activation by ATP. Regardless, developmental abnormalities of Kölliker's organ may lead to congenital hearing loss, considering that mutations in ion channels (hemichannels, gap junctions, and calcium channels) involved in Kölliker's organ activity share strong links with such types of deafness.


Subject(s)
Hair Cells, Auditory, Inner/pathology , Hearing Loss, Sensorineural/pathology , Kolliker-Fuse Nucleus/pathology , Receptors, Purinergic P2/metabolism , Cochlear Nerve/metabolism , Cochlear Nerve/pathology , Hair Cells, Auditory, Inner/metabolism , Hearing Loss, Sensorineural/etiology , Hearing Loss, Sensorineural/genetics , Humans , Kolliker-Fuse Nucleus/metabolism , Neurons/metabolism , Neurons/pathology , Receptors, Purinergic P2/genetics
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