Oncogenes and signal transduction pathways involved in the regulation of Na+ channel expression

Recent progress in neurobiology has revealed that proteins called 'neurotrophic factors' influence development, maintenance of function, and regeneration of neurons in vertebrate nervous system. These factors include the neurotrophin family, epidermal growth factor (EGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF), which are expressed in the nervous system. Effects of the neurotrophic factors are mediated through signal transduction pathways in which several cellular protooncogenes play intrinsic roles. Furthermore, studies on mechanisms coupling membrane events to gene activation have demonstrated that transsynaptic input via action potential and neurotransmitters, and membrane depolarization play an important role in the regulation of electrical activities in neurons during and after maturation. Voltage-dependent sodium (Na+) channels mediate an increase in permeability of Na+ during the initial, rapid phase of the action potential in neurons, and are considered to be important determinants of neuronal functions. Their synthesis and expression, therefore, are crucial aspects of neural differentiation and functions. In mammals, an array of functionally distinct Na+ channels arise, at least in part, through transcriptional regulation of the multiple genes that encode distinct Na+ channel alpha subunits (Na alpha). In this review, we discuss the potential roles of the protooncogenes in the nervous system, with particular emphasis on dynamic expression of the Na+ channel gene family.