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.