Neuronal nicotinic acetylcholine receptors: their properties and alterations in autosomal dominant nocturnal frontal lobe epilepsy.
Identification of genes coding for the neuronal nicotinic acetylcholine receptors (nAChRs) has allowed rapid progress in the field of neuroscience. Determination of a high-affinity binding site for nicotine that correlates with the expression of mRNAs coding for nAChRs as well as protein expression is the best demonstration for localization of these receptors. Reconstitution of functional nAChRs in cells following cDNAs injection opened new ways to study these receptors in isolation. Furthermore, the recent linkage analysis between a form of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) with a mutation in the gene coding for the alpha 4 subunit of the neuronal nAChRs constituted the first demonstration that alteration of these receptors may be at the origin of epileptic discharges. Physiological and pharmacological studies of these mutated receptors revealed that the two mutations so far identified in ADNFLE patient cause a loss of function. In this work we shall review, in the light of the latest findings, properties of control and mutated receptors and evaluate how their alteration can be at the origin of nocturnal seizures.
Bertrand
D
D
Dept of Physiology, CMU, Geneva 4, Switzerland.
D017034:Epilepsy, Frontal Lobe / Q000235:genetics* / Q000503:physiopathology*; D005799:Genes, Dominant; D006720:Homozygote; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000502:physiology; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000502:physiology*
D011978:Receptors, Nicotinic