Acetylcholine and alcohol sensitivity of neuronal nicotinic acetylcholine receptors: mutations in transmembrane domains.

Background: The effect of n-alcohols on glycine and gamma-aminobutyric acid type A receptors depends on two specific amino acids (AAs) located in the transmembrane domains (TM) 2 and 3. Our aim was to assess whether the corresponding AAs in the neuronal nicotinic acetylcholine receptor (nAChR) also formed a binding pocket for alcohols.

Methods: We made single AA substitutions in the homologous sites in rat neuronal nAChR alpha2 and alpha4 (alphaL261 and alphaL283) and expressed them in Xenopus laevis oocytes in combination with beta4 wild type.