The α3 and β4 subunits are most commonly expressed together in the same receptor subtype, with or without α5, in the peripheral nervous system (Wang et al. 1996). The β4 subunit is also found co-expressed with other α subunits in the central nervous system, with high expression in the medial habenula and interpeduncular nucleus (Salas et al. 2003). α3 and β4 containing receptors are involved in nicotine-induced seizures (Salas et al. 2004a) and β4 receptors may be important in anxiety-related behaviors (Salas et al. 2003). Oocytes containing β4 subunit polymorphisms showed varying differences in the EC50 for ACh activation (Liang et al. 2005). One variant, present in only the Caucasian sample, had a lower sensitivity to ACh, increased ACh EC50, and the slowest onset of desensitization. The other variants, found only in the African-American sample, had a higher sensitivity to ACh and lower EC50 (Liang et al. 2005). Mice null for the β4 nAChR subunit implanted with 13-day osmotic mini-pumps displayed significantly reduced mecamylamine-induced somatic (shaking, grooming, scratching, chewing) and non-somatic (hyperalgesia) symptoms of withdrawal, suggesting a role for this subunit in the appearance of nicotine withdrawal symptoms (Salas et al. 2004b).
