The role of G proteins in the activity and ethanol modulation of glycine-induced currents in rat neurons freshly isolated from the ventral tegmental area.
In freshly isolated neurons of the ventral tegmental area of young rats, we first examined the role of G proteins in the functional modulation of the glycine receptor (GlyR). GTP-gamma-S [guanosine-5'-0-(2-thiotriphosphate)] (2 mM) or GDP-beta-S [guanosine 5'-0-(2-thiodiphosphate)] (2 mM) was added to the pipette solution of whole-cell recordings to regulate G protein activities. GTP-gamma-S enhanced the amplitude of glycine-induced current (I(Gly)), suggesting modulation of GlyRs via a G protein-coupled pathway. GDP-beta-S suppressed I(Gly), suggesting that basal G protein activity positively modulates the GlyRs. We next examined effects of G proteins in ethanol potentiation of GlyR function. Activation of G proteins with 2 mM GTP-gamma-S attenuated, but did not eliminate, ethanol-induced potentiation of I(Gly). These results suggest that GTP-gamma-S and ethanol share the same pathway of activating GlyRs. When G proteins are maximally activated by GTP-gamma-S, the action of ethanol was partially occluded. When 2 mM GDP-beta-S was added in pipette solution, ethanol-induced potentiation of I(Gly) was significantly attenuated, suggesting that GDP-beta-S partially blocked the action of ethanol. However, the inability of GTP-gamma-S (or GDP-beta-S) to eliminate completely the potentiating effect of ethanol indicates that some other factors, in addition to G proteins, may also contribute to the action of ethanol on GlyRs.
Zhu
Li
L
Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Rutgers-UMDNJ Integrative Neuroscience Program, 185 South Orange Avenue, Newark, NJ 07103-2714, USA.
Ye
Jiang Hong
JH
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019204:GTP-Binding Proteins / Q000502:physiology*; D005998:Glycine / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000166:cytology*
D002492:Central Nervous System Depressants; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C023427:guanosine 5'-O-(2-thiodiphosphate); D019204:GTP-Binding Proteins; D000079:Acetaldehyde; D005998:Glycine