ROLE OF HERG K+ CHANNELS ENCODING GENES IN NEURONAL DEVELOPMENT

Neuronal and muscular electric activity is determined, in the adult, by the timed expression of ionic channels, in particular potassium channels, during prenatal development. Any alterations of this coordinated and timed , although still unexplored, expression pattern might determine the establishment of pathologies, like epilepsy and ataxia, characterised by alterations of neuronal excitability. Among the numerous potassium channels families, an important role in this field is exerted by members of a recently discovered family, the ERG family. While the role of ERG channels in the regulation of neuromuscular excitability is well demonstrated in Drosophila flies, their role in mammals is almost unknown. It is only known that ERG channels are expressed in human myocytes, and that point mutations of the human erg gene are the basis of an often fatal cardiac arrhythmia. The project here presented is aimed at determining the role of ERG encoding genes in neural system development, and in particular in the establishment of a correct neuromuscular excitability. For such study electrophysiological and biomolecular studies will be performed in order to define the role of erg channels in neuronal differentiation, with particular attention to the regulation of neural cell-microenvironment relationships. On the whole, such study might contribute to elucidate the definition of pathogenetic mechanisms leading to diseases characterised by alterations in neuronal excitability.