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.
Covernton
P J
PJ
Department of Physiology and Pharmacology, University of Strathclyde, Royal College, Glasgow.
Connolly
J G
JG
D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D014981:Xenopus
D002492:Central Nervous System Depressants; D011978:Receptors, Nicotinic; D000431:Ethanol