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Fast Ca(2+) Transients of Inner Hair Cells Arise Coupled and Uncoupled to Ca(2+) Waves of Inner Supporting Cells in the Developing Mouse Cochlea
Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice, inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca(2+) action potentials (APs), which stimulate the auditory pathway and guide maturation of neuronal circuits. During these early postnatal day...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6077211/ https://www.ncbi.nlm.nih.gov/pubmed/30104958 http://dx.doi.org/10.3389/fnmol.2018.00264 |
Sumario: | Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice, inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca(2+) action potentials (APs), which stimulate the auditory pathway and guide maturation of neuronal circuits. During these early postnatal days, intercellular propagating Ca(2+) waves elicited by ATP-induced ATP release are found in inner supporting cells (ISCs). It is debated whether IHCs are able to fire Ca(2+) APs independently or require a trigger by an ISC Ca(2+) wave. To identify the Ca(2+) transients of IHCs underlying Ca(2+) APs and to analyze their dependence on ISC Ca(2+) waves, we performed fast Ca(2+) imaging of Fluo-8 AM-loaded organs of Corti at P4/P5. Fast Ca(2+) transients (fCaTs) generated by IHCs were simultaneously imaged with Ca(2+) waves in ISCs. ISC Ca(2+) waves frequently evoked bursts consisting of >5 fCaTs in multiple adjacent IHCs. Although Ca(2+) elevations of small amplitude appeared to be triggered by ISC Ca(2+) waves in IHCs of Ca(v)1.3 knockout mice we never observed fCaTs, indicating their requirement for Ca(2+) influx through Ca(v)1.3 channels. The Ca(2+) wave-triggered Ca(2+) upstroke in wildtype IHCs occurred 0.52 ± 0.27 s later than the rise of the Ca(2+) signal in the adjacent ISCs. In comparison, superfusion of 1 μM ATP elicited bursts of fCaTs in IHCs starting 0.99 ± 0.34 s prior to Ca(2+) elevations in adjacent ISCs. PPADS irreversibly abolished Ca(2+) waves in ISCs and reversibly reduced fCaTs in IHCs indicating differential involvement of P2 receptors. IHC and ISC Ca(2+) signals were however unaltered in P2X2R/P2X3R double knockout or in P2X7R knockout mice. Together, our data revealed a fairly similar occurrence of fCaTs within a burst (56.5%) compared with 43.5% as isolated single fCaTs or in groups of 2–5 fCaTs (minibursts). We provide evidence that IHCs autonomously generate single fCaTs and minibursts whereas bursts synchronized between neighboring IHCs were mostly triggered by ISC Ca(2+) waves. Neonatal IHCs thus spontaneously generate electrical and Ca(2+) activity, which is enhanced and largely synchronized by activity of ISCs of Kölliker’s organ indicating two sources of spontaneous activity in the developing auditory system. |
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