Papel De Los Receptores De Glutamato Durante La Diferenciación Neuronal

L-glutamate (Glu) is the main excitatory neurotransmitter in the Central Nervous System (CNS). The glutamate receptors (GluRs) are distributed in all CNS regions and they have been classified in two big families. The first big family is formed by the ionotropic glutamate receptors (iGluRs) or ligand-gated ion channels, which allow selective crossing of ions through selective ion channels permeable to Ca2+, Na+ and K+. Depending of the electrophysiological and pharmacological properties of these receptors, they are classified in three families: the α-amino-3-hydroxi-5-methyl4-isoxazol-propionic acid (AMPA) receptors, the kainate receptors (KA) and the N-methyl-D-aspartate (NMDA) receptors. The general structure of iGluRs, consists of an extracellular amino terminal domain (NTD), two ligand-binding domains (S1 and S2), three trans-membrane segments (TM1, TM2 and TM3), a re-entrant pore loop and an intracellular carboxyl terminal domain (CTD). They are generally assembled into a tetrameric structure, formed by hetero-oligomeric integral protein subunits, which are encoded by different genes. The AMPA receptors family includes GluR-1, GluR-2, GluR-3 and GluR-4; the kainate receptors family comprises GluR-5, GluR-6, GluR-7, K1 and K2; and the NMDA receptors family is conformed by NR1, NR2 (NR2A-D) and NR3 (NR3A and 3B). In addition, alternative splicing of the primary transcripts increases the diversity of ionotropic receptor variants. The second great family is composed by the metabotropic glutamate receptors (mGluRs), which are associated to G-proteins that work through intracellular signaling generated by second messengers (inositol 3-phosphate, diacylglycerol and cAMP). As a general characteristic of their structure, the mGluRs have a large extracellular NTD, seven transmembrane passages connected by intracellular and extracellular loops, and an intracellular CTD. The mGluRs are divided in three groups: class I receptors include mGluR1 and mGluR5; class II receptors include mGluR2 and mGluR3; and class III receptors include mGluR4, mGluR6, mGluR7 and mGluR8. Generally, class I receptors are coupled to a Gq associated to phosphoinositides hydrolysis and function as postsynaptic receptors with an increased neuronal excitability. Class II and III receptors are coupled to Gi/Go, and are associated with adenylyl cyclase inhibition and function as pre-synaptic receptors diminishing neurotransmitter release. As in the case of iGluRs, there are many isoforms for mGluRs generated by alternative splicing of the pre-mRNA. PAPEL DE LOS RECEPTORES DE GLUTAMATO DURANTE LA