New functions for nicotinic acetylcholine receptors?

Although the neuronal nicotinic acetylcholine receptor is found in most parts of the brain, not much is known about its functional significance. At least ten different subunits are expressed in the central nervous system, theoretically able to give rise to more than a thousand different receptor subtypes. Despite, or perhaps because of, this astonishing diversity, the biological role of this receptor type remains to be investigated. It has recently been found that a mutated alpha4-subunit is associated with an inherited epilepsy syndrome. A missense mutation replacing a serine in position 248 of the second transmembrane domain by phenylalanine leads to hypoactivity of the receptor due to accelerated desensitization and delayed resensitization. Thus, for the first time a link between a human disease and a mutated neuronal nicotinic acetylcholine receptor has been found, pointing to a possible involvement of this ligand-gated receptor family in the modulation of brain excitability levels.