title: The neuronal nicotinic acetylcholine receptor in some hereditary epilepsies.
abstract: Recent advances in human genetics and in the neurobiology of neurotransmitter receptors and channels have led to the discovery of specific genes associated with hereditary epileptic phenotypes. All the genes identified to date code for ligand- and voltage-gated ion channels. Some clinically rare idiopathic epilepsies are associated with mutations in genes coding for different neuronal nicotinic acetylcholine receptor (AChR) subunits. Distinct alpha subunits are found in the brain and in the peripheral nervous system, and structural, non-alpha subunits like beta2 and beta4 confer different properties to neuronal receptors. Thus, the final properties of the oligomeric AChR depend on the different combinations of alpha and beta subunits. Most mutations found so far occur in the alpha4 chain, the most abundant subunit in the central nervous system. Specifically, the identification of mutations in the alpha4 subunit of neuronal AChR in human benign familial neonatal convulsions (BFNC) and autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) raise the possibility that the observed gene defects are linked (causatively) with these two diseases or, alternatively, that AChR alpha4 mutants increase the probability of epileptic discharges. We discuss testable hypotheses for unraveling the pathophysiology of these two disorders associated with AChR mutations.
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Argentina. rtfjb1@criba.edu.ar
authors.forename: F J
authors.initials: FJ
authors.lastname: Barrantes
authors.forename: E
authors.initials: E
authors.lastname: Aztiria
authors.forename: M B
authors.initials: MB
authors.lastname: Rauschemberger
authors.forename: A
authors.initials: A
authors.lastname: Vasconsuelo
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004827:Epilepsy / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D017433:Protein Structure, Secondary; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics*; D012640:Seizures / Q000235:genetics
chemical_list: D011978:Receptors, Nicotinic