KCNQ2/3 POTASSIUM CHANNELS AS MOLECULAR GATEWAYS FOR NEURONAL EXCITABILITY: FROM SCREENING AND FUNCTIONAL ANALYSIS OF BENIGN FAMILIAL NEONATAL CONVULSIONS-CAUSING MUTATIONS TO ANIMAL MODELS OF IDIOPATHIC EPILEPSIES

Epilepsy affects 0.5-1% of the general population, and is characterized by convulsive manifestations which can remain focal or spread to all cortical regions of the brain. Although most epilepsies are idiopathic, meaning that they do not recognize a specific triggering mechanism or hereditary transmission, about 1-2% of epilepsies are genetically-determined. Within these hereditary forms, Benign Neonatal Familial Convulsions (BNFC) have a typical onset in the first week of postnatal life that end spontaneously by the age of six months, without affecting the neurological or psychological development of the affected child. The present research project will serve a double purpose. On one hand, it will provide clinically-relevant information on the disease, by identifying novel mutations in the affected genes and by establishing correlation between the severity of the disease and the underlying genetic alteration. On the other hand, by means of an integrated approach of different basic science methodologies, the functional consequences of such genetic alterations will be defined, with particular focus on the functional alterations (biophysical, pharmacological, and biochemical) they induce on the activity of the cellular systems where malfunctioning genes are implicated. It seems possible to foresee that the achievement of the proposed aims, will provide momentum to the improvement of the clinical and basic science knowledge about the pathogenesis, the pathophysiology and the pharmacology of BFNC. Furthermore, it seems likely that the results achieved will be of interest not only to those patients affected by BFNC, but also impact on the large population of patients suffering from idiopathic epilepsy, for whom optimal pharmacological treatments are still missing.