Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters’ Cells in the Organ of Corti in Hearing BALB/c Mice

Moysan, Louise and Fazekas, Fruzsina and Fekete, Ádám and Köles, László and Zelles, Tibor and Berekméri, Eszter (2023) Ca2+ Dynamics of Gap Junction Coupled and Uncoupled Deiters’ Cells in the Organ of Corti in Hearing BALB/c Mice. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 (13). No.-11095. ISSN 1661-6596 (print); 1422-0067 (online)

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Abstract

ATP, as a paracrine signalling molecule, induces intracellular Ca2+ 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 Ca2+ waves via diffusion of Ca2+ mobilising second messenger IP3 between neighbouring cells. We have compared the ATP-evoked Ca2+ transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca2+ transients in DCs located in the apical and middle turns of the hemicochlea preparation of BALB/c mice (P14–19). Octanol had no effect on Ca2+ 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 Ca2+ dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca2+ transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca2+ pump expressions and in IP3–Ca2+ 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 IP3-mediated Ca2+ signalling inhibition by CBX cannot be excluded.

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