Differential modulation of rat neuronal nicotinic receptor subtypes by acute application of ethanol

1 We have studied the effects of acute ethanol (EtOH) exposure on the agonist responses of rat neuronal nicotinic receptors expressed in Xenopus oocytes by means of voltage clamp techniques. 2 In some cells, agonist-induced current responses with the alpha 3 beta 4 subunit combination could be either significantly potentiated or inhibited (range 25% to 237% of control response) by low ethanol concentrations (1-30 mM). At high ethanol concentrations (100-300 mM) robust potentiations were observed (range 135% to 305% of control). 3 The low EtOH concentration effects on the alpha 3 beta 4 subtype exhibited tolerance with repeated EtOH exposure. 4 In general, the alpha 3 beta 2, alpha 4-1 beta 2 and alpha 4-1 beta 4 subunit combinations were less sensitive to low concentrations of ethanol, but respectively showed potentiations of up to 178%, 226% and 154% at high EtOH concentrations. 5 The alpha 7 homomeric receptor was also relatively insensitive at low EtOH concentrations. At high EtOH concentrations, potentiations, inhibitions or no alteration of control agonist response were observed (range 88% to 141% of control). 6 We conclude that all the neuronal nicotinic receptor subunit combinations tested here can be modulated by high concentrations of EtOH in a rapidly reversible manner. This modulation may underlie some of the behavioural effects of ethanol. The alpha 3 beta 4 subunit combination may be especially sensitive to modulation by low EtOH concentrations. This remarkable sensitivity and plasticity of nicotinic receptors may contribute to a process of mutual reinforcement in nicotine and alcohol addiction.