Ethanol Potentiation of Glycine Receptors Expressed in Xenopus Oocytes Antagonized by Increased Atmospheric Pressure

Abstract

This is the first use of hyperbarics to investigate the mechanism of action of ethanol in recombinant receptors. The findings indicate that pressure directly and selectively antagonizes ethanol potentiation of alpha(1)GlyR function in a reversible and concentration- and pressure-dependent manner. The sensitivity of ethanol potentiation of GlyR function to pressure antagonism indicates that ethanol acts by a common, pressure-antagonism-sensitive mechanism in GlyRs and GABA(A)Rs. The findings also support the hypothesis that ethanol potentiation of GlyR function plays a role in mediating the sedative-hypnotic effects of ethanol.

Low-dose alcohol actions on α4β3δ GABA A receptors are reversed by the behavioral alcohol antagonist Ro15-4513

“…Other potential alcohol targets that might contribute to Ro15-4513-insensitive acute alcohol actions are NMDA (1), glycine (2), and adenosine receptors (65), and voltage-and Ca 2ϩ -activated (BK) potassium channels (66,67). In addition, we show here that the Ro15-4513-insensitive alcohol action on ␣4␤3␦ GABA A R is abolished by a mutation (␤3N265M) in the ␤3 subunit.…”

“…Neurotransmitter receptors for GABA, NMDA and glycine, and G protein-gated K ϩ channels have been identified as potential alcohol targets that are sensitive to intoxicating alcohol concentrations (1)(2)(3)(4). GABA A receptors (GABA A Rs) have long been suspected to be important mediators of alcohol effects (5, 6) because benzodiazepines (BZs) and barbiturates, classic GABA A R agonists, share common pharmacological properties with ethanol, such as sedativehypnotic, anti-anxiety, and motor in-coordinating and anticonvulsant effects and have additive, possibly even synergistic effects, when taken together with ethanol (7).…”

Transmembrane voltage potential controls embryonic eye patterning inXenopus laevis

“…We used the constitutively conductive EXP1 cation channel (Beg and Jorgensen, 2003) and the glycine-gated chloride channel (GlyR) (Davies et al, 2003), which can be permanently activated by the specific GlyR opener Ivermectin (IVM) (Shan et al, 2001). The use of two different molecular reagents (channels that share no sequence or structural homology and have in common only their effect on membrane potential) specifically tested the role of V mem per se, independent of possible other functions of a particular channel protein or ion species.…”

Synaptic Effects Induced by Alcohol

“…Potentiation is consistently greater at receptors containing the α1 subunit (Davies et al 2003;Mascia et al 1996;Mihic et al 1997), at least when expressed in xenopus laevis oocytes (Valenzuela et al 1998b, although see McCool et al 2003Yevenes et al 2008). Receptors containing the α2 subunit also exhibit EtOH potentiation , but may be less sensitive than those containing the α1 subunit (Mascia et al 1996).…”