title: A novel choline-sensitive nicotinic receptor subtype that mediates enhanced GABA release in the chick ventral lateral geniculate nucleus.
abstract: Nicotinic acetylcholine receptors modulate the release of GABA, glutamate, acetylcholine and dopamine in the brain. Here we describe a novel choline-sensitive nicotinic acetylcholine receptor that mediates enhanced GABA release in the chick ventral lateral geniculate nucleus. Whole-cell recordings in slices demonstrated that choline (0.03-10 mM), generally considered an alpha7-selective agonist, and carbachol (3-300 microM), a non-selective cholinergic agonist, both increased the frequency of spontaneous GABAergic events in ventral lateral geniculate nucleus neurons. Tetrodotoxin (0.5 microM) partially reduced responses to carbachol, but eliminated responses to choline. During long-term (5 min) exposure to choline the GABA enhancement was maintained until choline was washed out. Choline (300 microM) enhanced the frequency of spontaneous GABAergic events by 4.28-fold in control artificial cerebrospinal fluid. This choline-mediated enhancement was significantly reduced by the following nicotinic acetylcholine receptor antagonists: 1 microM dihydro-beta-erythroidine (1.49-fold increase, P<0.001), 1 microM methyllycaconitine (1.53-fold, P<0.001) and 0.2 microM alpha-conotoxin ImI (1.84-fold, P<0.001). In contrast, no significant change was seen in the presence of 0.1 microM dihydro-beta-erythroidine, 0.1 microM methyllycaconitine, 0.1 microM alpha-bungarotoxin, 0.1 microM alpha-conotoxin MII, 0.1 microM kappa-bungarotoxin, or 1 microM alpha-conotoxin AuIB. These results indicate that choline, at concentrations as low as 100 microM, activates a nicotinic acetylcholine receptor that is distinct from the classical alpha7 nicotinic acetylcholine receptors previously known to be activated by choline.
authors.affiliation: Department of Pharmacology, The George Washington University, School of Medicine and Health Sciences, 2300 Eye Street, N.W., Washington, DC 20037, USA. phmjzg@gwumc.edu
authors.forename: J-Z
authors.initials: JZ
authors.lastname: Guo
authors.forename: V A
authors.initials: VA
authors.lastname: Chiappinelli
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002642:Chick Embryo; D002794:Choline / Q000378:metabolism* / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005829:Geniculate Bodies / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018679:Cholinergic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D002794:Choline