Ca 2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters' Cells in the Organ of Corti in Hearing BALB/c Mice.

International journal of molecular sciences(2023)

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摘要
ATP, as a paracrine signalling molecule, induces intracellular Ca elevation via the activation of purinergic receptors on the surface of glia-like cochlear supporting cells. These cells, including the Deiters' cells (DCs), are also coupled by gap junctions that allow the propagation of intercellular Ca waves via diffusion of Ca mobilising second messenger IP between neighbouring cells. We have compared the ATP-evoked Ca transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca transients in DCs located in the apical and middle turns of the hemicochlea preparation of / mice (P14-19). Octanol had no effect on Ca signalling, while CBX inhibited the ATP response, more prominently in the middle turn. Based on astrocyte models and using our experimental results, we successfully simulated the Ca dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca pump expressions and in IP-Ca release mechanisms. The cochlear turn-dependent effect of CBX might be the result of the differing connexin isoform composition of GJs along the tonotopic axis. The contribution of IP-mediated Ca signalling inhibition by CBX cannot be excluded.
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