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

ATP, as a paracrine signalling molecule, induces intracellular Ca(2+) 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(2+) waves via diffusion of Ca(2+) mobilising second messenger IP(3) between neighbouring cells. We have compared the ATP-evoked Ca(2+) transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca(2+) 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 Ca(2+) 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(2+) dynamics in DCs in different cochlear regions. The mathematical model reliably described the Ca(2+) transients in the DCs and suggested that the tonotopical differences could originate from differences in purinoceptor and Ca(2+) pump expressions and in IP(3)–Ca(2+) 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(3)-mediated Ca(2+) signalling inhibition by CBX cannot be excluded.