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Alcohol Modulation of Neuronal Nicotinic Acetylcholine Receptors Is α Subunit Dependent
Author(s) -
Zuo Yi,
Kuryatov Alexander,
Lindstrom Jon M.,
Yeh Jay Z.,
Narahashi Toshio
Publication year - 2002
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2002.tb02605.x
Subject(s) - acetylcholine receptor , nicotinic agonist , receptor , acetylcholine , long term potentiation , chemistry , biophysics , stimulation , mechanism of action , neuroscience , biochemistry , pharmacology , microbiology and biotechnology , biology , in vitro
Background: We have previously shown that n‐alcohols exert a dual action on the α 4 β 2 ‐type neuronal nicotinic acetylcholine (ACh) receptors (AChRs), with shorter‐chain alcohols potentiating and longer‐chain alcohols inhibiting ACh‐induced currents. Ethanol potentiates the current in α 4 β 2 receptors, yet it has little or no effect on the α 3 β 2 receptors. Because the α 4 AChRs are present predominantly in the brain, whereas the α 3 AChRs are present predominantly in the peripheral ganglia, the differential action of ethanol on the α 4 β 2 and α 3 β 2 AChRs may contribute to its differential effects on the brain and the peripheral nervous system. The purpose of this study was to characterize the actions of alcohols on an α 3 ‐containing nicotinic receptor and to further understand the mechanism underlying the differential action of ethanol on the two receptor subtypes. Methods: ACh‐induced currents were recorded from human α 3 β 2 AChRs recombinantly expressed in human embryonic kidney tsA201 cells by using the whole‐cell patch clamp technique. Results: The ACh‐induced currents in the α 3 β 2 receptors were potentiated by methanol and inhibited by longer‐chain alcohols. The transition point from potentiation to inhibition and the cutoff point were both shifted to shorter alcohols in the α 3 β 2 AChR compared with the α 4 β 2 AChR. This explains why ethanol, which was at the transition point, has little or no effect on the α 3 β 2 AChR. Conclusions: The α 3 β 2 AChRs are insensitive to ethanol because ethanol is at the transition point from potentiation to inhibition among n‐alcohols with different carbon‐chain lengths. The differential action on the α 4 β 2 and α 3 β 2 AChRs may explain the differential action of ethanol on the central nervous system.