FUNCTIONAL STUDY OF EPILEPTOGENIC NA+ CHANNEL MUTATIONS IN TRANSFECTED NEURONS AND ANIMAL MODELS

Our study aims to the elucidation of the functional effects of the mutations that cause genetically transmitted epilepsies. Epilepsy is a condition in which a person has recurrent seizures due to abnormal and hypersynchronous discharges from a group of central nervous system neurons. Depending on the cerebral area involved by the discharges, a seizure can have various manifestations, ranging from convulsions to sensory experiences. Epileptic discharges often spread to large brain areas and cause alteration of consciousness. There are many forms and causes of epilepsy. Recently the genetic causes of some epilepsy syndromes have been discovered and mutations of voltage-gated Na+ channels are the most common. They can also cause familial hemiplegic migraine. Voltage-gated sodium channels are proteins of the cell membrane that are responsible for the generation and propagation of action potentials: the momentary change in neuronal membrane electrical potential forming the neuronal discharges. It is important to understand the functional effects of the mutations of sodium channels to reveal the pathogenic mechanisms, improve diagnosis and develop therapies. However, the functional effects of most of them is not clear yet, because they have been studied with experimental models that do not reproduce real physiopathological conditions and neuronal properties. We will study epileptogenic and migraine mutations of Na+ channels using transfected neurons and animal models, experimental systems that preserve neuronal properties and physiopathological conditions. Thus, we will shed light on their pathogenic mechanism, improving early diagnosis and facilitating the development of effective therapies.