Ca2+ signals:
Molecular Mechanisms and Integrative Functions Collaborative Research Center 894

Project A8 - Jutta Engel

Calcium channel complexes in inner hair cells

Voltage-gated Ca2+ channels (VGGCs) of mammalian inner hair cells (IHCs) mediate sound-evoked synaptic transmitter release. In a critical development period before the onset of hearing, VGCCs are transiently upregulated for generating Ca2+ action potentials and controlling gene expression. Congenitally reduced Ca2+ currents cause an impaired IHC phenotype and hearing loss. VGCCs of IHCs consist of the pore-forming subunit Cav1.3, which co-assembles mostly with auxiliary subunits β2 and α2δ. They have unusual gating and inactivation properties.

We aim at defining the role of Cav1.3 and Cavβ2 splice variants for properties of Ca2+ currents and the function of IHCs. The recently discovered role of α2δ2 in the spatial coupling of presynaptic Cav1.3 channels with postsynaptic proteins will be investigated in detail. Using conditional (Cre-loxP) mouse models with hair cell-specific deletion of Cav1.3, Cavβ2 or α2δat either embryonic age or around onset of hearing we will dissect their impact for development and mature IHC phenotype and hearing function. We will employ a combination of electrophysiology, molecular biology, high-resolution immunofluorescence techniques and hearing measurements.