ChemBIon project description:

Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, the molecular correlate of the hyperpolarization-activated inward current (Ih), have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The four subtypes (HCN1-4) all differ in their biophysical and modulatory properties and show differential distribution in the brain. Direct sensitivity to cAMP originating from a C-terminal cyclic nucleotide binding domain (CNBD) is the central modulatory motif of HCN channels. More recently the tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b), a brain-specific accessory subunit which binds to the C-terminus, was found to be important for HCN channel regulation. This project aims to achieve a better understanding of the cell type-specific function of HCN channel isoforms and their interaction with auxiliary subunits under normal and inflammatory conditions. In addition, the restorative potential of HCN channel activators under conditions of reduced channel function will be assessed in brain slices. As a necessary bridge for the future use of channel modulators in disease models, their effects in the living brain will be proven by electrophysiological recordings in vivo combined with intrathalamic substance application.