Minimal model analyzing response of glycine receptors expressed in Xenopus oocyte: inhibition by a lipid hydroperoxide.
Glycine receptor (GlyR) was expressed in Xenopus oocytes by injecting rat brain mRNA. Glycine (Gly)-elicited responses in the oocyte were measured by the voltage-clamping method. The following measurements were made to establish the relationship between Gly concentration and the current: 1) Gly-induced membrane current before desensitization, 2) Gly-induced membrane current after desensitization equilibrium, 3) fraction of the active form of the receptor after desensitization equilibrium, 4) rate of recovery of the desensitized receptors upon removal of Gly. These results were analyzed on the basis of the minimal model proposed for nicotinic acetylcholine and gamma-aminobutyric acid A receptor. The equilibrium and rate constants of the model were evaluated for GlyR. The effects of procaine and 13-L-hydroperoxylinoleic acid (LOOH) on GlyR were examined electrophysiologically. LOOH noncompetitively inhibited the receptor with the inhibition constant of 27 microM, while 1 mM procaine, a local anesthetic, did not inhibit GlyR at all.
Aoshima
H
H
Department of Chemistry, Faculty of Liberal Arts, Yamaguchi University.
Inoue
Y
Y
Ueda
E
E
Kitagawa
M
M
Nishino
T
T
D000818:Animals; D001921:Brain / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005998:Glycine / Q000494:pharmacology; D007700:Kinetics; D008041:Linoleic Acids / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D018733:Nicotinic Antagonists; D009865:Oocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D011343:Procaine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000502:physiology*
D008041:Linoleic Acids; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D011343:Procaine; C032890:13-hydroperoxylinoleic acid; D005998:Glycine