Cellular-Distribution Of The Messenger-Rna For The Alpha-7 Subunit Of The Nicotinic Acetylcholine-Receptor In The Human Cerebral-Cortex

Central nicotinic acetylcholine receptors (nAChRs) are ligand-gated cationic channels characterized by a wide pharmacological and molecular diversity depending on the subunits involved. Recently a new type of a nicotinic acetylcholine receptor channel, highly permeable to calcium, consisting of alpha 7 subunits which bear a binding site for the snake venom alpha-bungarotoxin has been described. alpha-bungarotoxin binding sites have previously been localized in the human and rat brain. Immunohistochemistry has revealed the presence of alpha 7 subunits in the rodent CNS. Presently we have applied digoxigenin-labeled RNA probes to localize alpha 7 mRNA in human brain using autopsy samples of prefrontal (Area 10) and motor cortex (Area 4). alpha 7 transcripts are expressed in numerous neurons throughout both cortical regions. Mainly pyramidal-like neurons of layers II/III, V, and VI were labeled. In contrast to our previous studies on the localization of alpha 3 and alpha 4 transcripts, only a few giant pyramidal neurons in A4 but a rather high number of layer I neurons in A4 and A10 expressed alpha 7 mRNA. The study shows that nicotinic receptor subunit mRNAs are distributed in a subunit- and area-specific manner in the human cerebral cortex. These findings will be of importance as to the selective, ligand-mediated stimulation of nicotinic receptor subtypes as a possible tool to improve cholinergic transmission in neurodegenerative disorders like Alzheimer's disease. (C) 1995 Wiley-Liss, Inc.