The combination of voltage-gated ion channels residing in a neuron’s membrane determines its activity profile, or ‘intrinsic excitability’. Most neuron types display a very robust intrinsic excitability signature. Moreover, there is evidence that perturbation of ion channels induces homeostatic regulation of other ion channels, thereby maintaining neural excitability. Channelopathies are a group of diseases resulting from ion channel dysfunction leading to cognitive impairments, epilepsy or migraine. It is currently largely unknown which molecular mechanisms maintain neural excitability in a homeostatic fashion, and why these mechanisms are unable to compensate for ion channel dysfunction in the context of channelopathies.
The central goal of this project is to establish links between homeostatic regulation of neural excitability and channelopathies.
Recent findings & current work
We are in the process of investigating neural excitability and ion channel biophysics in neurons derived from patients with intellectual disability carrying de novo mutations in SCN2A, the gene coding for the alpha-subunit of the voltage-gated sodium channel type 2, in the context of the CRPP Praeclare.