Effects of ethanol on ion channels.
Ion channels play critical roles in nervous system function, from initiating rapid synaptic activity to propagation of action potentials. Studies have indicated that many of the effects of ethanol on the nervous system are likely caused by the actions of ethanol on ion channels. Ion channels are multimeric structures that gate ions through subtle changes in tertiary structure. Ethanol readily enters molecular sites within multimeric ion channels, modifying intermolecular forces and bonds that are important for the open-close-inactivation kinetic properties of channels. The diversity of channel composition caused by the multimeric structure results in subtypes of channels that have a spectrum of sensitivity to ethanol that translates into brain regional differences in ethanol sensitivity, in part caused by differences in ion channel subunit composition. Ethanol has been shown to affect both receptor-activated ion channels and voltage-gated ion channels. The acute intoxicating and incoordinating effects of ethanol are probably related to inhibition of subtypes of NMDA-glutamate receptor ion channels and potentiation of certain subtypes of GABAA receptor ion channels. Effects on these channels, as well as glycine, nicotinic cholinergic, serotonergic, and other ion channels, likely contribute to the euphoric, sedative, and other acute actions of ethanol. Changes in ion channel subunit composition, density, and properties probably also contribute to ethanol tolerance, dependence, withdrawal hyperexcitability, and neurotoxicity. A substantial number of studies have implicated glutamate NMDA receptor, GABAA, and L-type voltage-gated calcium channels in the adaptive changes in the brain during chronic ethanol exposure. The diversity of ion channels subunits, their prominent role in brain function, and ethanol action are likely to make them important contributors to alcoholism and alcohol abuse.
Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill 27599, USA.
F T
FT
Crews
A L
AL
Morrow
H
H
Criswell
G
G
Breese
D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects
D007473:Ion Channels; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017470:Receptors, Glutamate; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic; D000431:Ethanol