| Autor: |
Yen, P., De Faveri, F., Ceriani, F., Marcotti, W. |
| Předmět: |
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| Zdroj: |
Journal of Hearing Science; Sep2024, Vol. 14 Issue 3, p115-116, 2p |
| Abstrakt: |
Introduction: Developing cochlear inner hair cells (IHCs) elicit sensory-independent Ca2+ action potentials (APs) that propagate along the auditory pathway and is required for the maturation of the IHCs and for the refinement of the neural circuitry. The AP activity in IHCs is believe to the synchronized by spontaneous ATP-induced Ca2+ waves originating in the non-sensory supporting cells (SCs). This ATP signalling triggers fluid secretion from the SCs by activating Ca2+-activated Cl- channel (TMEM16A), which has been reported having bipolar influence on the IHC excitability. Whether TMEM16A channels are involved in the functional maturation of IHCs is still unclear. Material and methods: We used conditional Tmem16afl/ flPlp1-cre mice in which the expression of TMEM16a was downregulated specifically in the inner phalangeal and inner border cells (IPhC and IBC), which are the SCs adjacent to the IHCs. Cell-attached path-clamp electrophysiology was used to monitor the SAP activity from ex-vivo cochlear tissue, while whole-cell patch-clamp was used to record current and voltage responses in pre- and post-hearing IHCs. Results: We showed that the absence of TMEM16A in IPhC and IBC significantly prolonged the inter-spike intervals (ISIs) of spontaneous APs in the IHCs. High-frequency burst of APs (≥10 Hz) in IHCs were almost completely eliminated in the absence of TMEM16a channels. Calcium imaging also revealed a significantly reduced correlation in APs between nearby IHCs from Tmem16afl/flPlp1-cre mice. Although the IHCs from Tmem16afl/flPlp1-cre mice appeared to experience an initial delay in the maturation of their basolat-eral membrane currents, they were indistinguishable from control IHCs. Conclusions: We showed that IPhCs and IBCs mediate the synchronization of APs in nearby IHCs and that the activation of TMEM16A channels is critical to elicit high-frequency burst (>10 Hz) in developing IHCs. We also found that IHCs from Tmem16afl/flPlp1-cre mice show a delay in their maturation, highlighting the possible role of ATP signalling from the SCs is driving the normal development of IHCs. [ABSTRACT FROM AUTHOR] |
| Databáze: |
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