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Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear.

ABSTRACT: Connexin gap junctions play an important role in hearing function, but the mechanism by which this contribution occurs is unknown. Connexins in the cochlea are expressed only in supporting cells; no connexin expression occurs in auditory sensory hair cells. A gap junctional channel is formed by two hemichannels. Here, we show that connexin hemichannels in the cochlea can release ATP at levels that account for the submicromolar concentrations measured in the cochlear fluids in vivo. The release could be increased 3- to 5-fold by a reduction of extracellular Ca2+ or an increase in membrane stress, and blocked by gap junctional blockers. We also demonstrated that extracellular ATP at submicromolar levels apparently affected outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining cochlear sensitivity to sound stimulation in mammals. ATP reduced OHC electromotility and the slope factor of the voltage dependence and shifted the operating point to reduce the active amplifier gain. ATP also reduced the generation of distortion products. Immunofluorescent staining showed that purinergic receptors P2x2 and P2x7 were distributed on the OHC surface. Blockage of P2 receptors eliminated the effect of ATP on the OHC electromotility. The data revealed that there is a hemichannel-mediated, purinergic intercellular signaling pathway between supporting cells and hair cells in the cochlea to control hearing sensitivity. The data also demonstrated a potential source of ATP in the cochlea.

SUBMITTER: Zhao HB

PROVIDER: S-EPMC1317927 | biostudies-literature | 2005 Dec

REPOSITORIES: biostudies-literature

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Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear.

Zhao Hong-Bo HB Yu Ning N Fleming Carrie R CR

Proceedings of the National Academy of Sciences of the United States of America 20051212 51

Connexin gap junctions play an important role in hearing function, but the mechanism by which this contribution occurs is unknown. Connexins in the cochlea are expressed only in supporting cells; no connexin expression occurs in auditory sensory hair cells. A gap junctional channel is formed by two hemichannels. Here, we show that connexin hemichannels in the cochlea can release ATP at levels that account for the submicromolar concentrations measured in the cochlear fluids in vivo. The release c ...[more]

PMID: 16344488

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Project description:Although recent advances in magnetic resonance imaging (MRI) techniques have contributed to the detection of tiny lesions in the internal auditory canal (IAC) that may be responsible for sudden sensorineural hearing loss (SSNHL), there have been relatively few studies on the clinical characteristics of intra-labyrinthine hemorrhage (ILH) and labyrinthitis versus those regarding IAC tumors. Our purpose was to investigate the frequency of those IAC lesions on MRI and their clinical characteristics. Initial MRIs of 200 patients with SSNHL (93 men, 107 women; mean age = 48.61 years, range: 18-84 years), as well as detailed clinical histories, audiological examinations, and thyroid function, lipid battery, and serological tests (for viral agents and autoimmune disease), were performed. All patients were hospitalized at the time of diagnosis of SSNHL and were administered the same treatment protocol. Patients were divided into idiopathic and secondary groups according to their MRI results. After discharge, they underwent follow-up audiometry and clinical examination at predetermined intervals (2 weeks, 1, 2, 4, and 6 months, and 1 and 2 years). Propensity score-matching and receiver operating characteristics curves of the initial parameters were used for estimating clinical characteristics. Of the 200 patients, 25 (12.55%) who had abnormal findings suggesting inner ear lesions on MRI were assigned to the secondary SSNHL group; within this group, 10 patients (10/200, 5%) had a tumor invading the IAC, 7 (7/200, 3.5%) had ILH, 6 (6/200, 3%) had labyrinthitis, and 2 (1%) had a structural deformity of the IAC. The secondary group showed significantly poor recovery of hearing function compared with that in the idiopathic group. Patients with ILH or labyrinthitis showed prognoses that were equally poor as those of patients with tumors in the secondary group. Additionally, patients with such lesions showed significant canal paresis on the lesion side at an early stage and a high prevalence of benign paroxysmal positional vertigo (BPPV). In conclusion, the prevalence of non-tumorous lesions on MRI represents common findings and showed a poorer treatment response than that of vestibular Schwannoma in patients with SSNHL. Abnormal canal paresis (cut-off value of 35% on the lesioned side, sensitivity 65.2% and specificity 67%), spontaneous nystagmus directed to the contralesional side, and positional vertigo would be the clinical presentation of SSNHL with IAC lesions, in which the presence of acute prolonged vertigo or positional vertigo compatible with BPPV suggests the possibility of a non-tumorous lesion, such as ILH or a labyrinthitis rather than an IAC tumor.

Dataset Information

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear.

Publications

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear.

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