title: Rapid activation of presynaptic nicotinic acetylcholine receptors by nerve-released transmitter.
abstract: Nicotine's ability to enhance neurotransmitter release has implicated presynaptic nicotinic acetylcholine receptors (nAChRs) in synaptic modulation, but there aze few examples where presynaptic nAChRs are known to be activated by nerve-released transmitter. We searched for endogenous activation of presynaptic nAChRs in the calyceal nerve terminals of the chick ciliary ganglion by imaging presynaptic calcium transients using dextran-coupled indicator dyes. The amplitude of Ca(+)signals recorded in individual nerve terminals was frequency dependent over 2-50 Hz. Calcium transients evoked by stimulation of the preganglionic nerve were significantly reduced (approximately 10-15%) by the nonspecific nAChR antagonist d-tubocurarine (d-TC; 100 microM) and the alpha7-specific antagonist methyllycaconitine (20-50 nM) but were not affected by 10 microM dihydro-beta-erythroidine, which should inhibit several non-alpha7 nAChRs. Feedback was rapid and did not require a stimulation-dependent build-up of transmitter, as d-TC and MLA reduced the amplitude of the first calcium transient in a 2-Hz train. Choline is an agonist at alpha7 nAChRs but is not the sole agonist in this system, as inhibition of acetylcholinesterase by echothiophate failed to reduce calcium transients. These results show that nerve-released acetylcholine (ACh) feeds back onto presynaptic alpha7 nAChRs to enhance calcium signals within the terminal. This feedback may help maintain the high rate of transmission at this cholinergic synapse.
authors.affiliation: Department of Stomatology, University of California, San Francisco, CA 94143, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Rogers
authors.forename: Peter B
authors.initials: PB
authors.lastname: Sargent
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials / Q000187:drug effects; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002642:Chick Embryo; D002794:Choline / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004456:Echothiophate Iodide / Q000494:pharmacology; D004558:Electric Stimulation; D005456:Fluorescent Dyes / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D066298:In Vitro Techniques; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D009930:Organic Chemicals; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D002800:Cholinesterase Inhibitors; D003911:Dextrans; C409648:Fluo 4; D005456:Fluorescent Dyes; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; C403124:Oregon Green BAPTA-dextran; D009930:Organic Chemicals; D011978:Receptors, Nicotinic; D014966:Xanthenes; D002104:Cadmium; D004456:Echothiophate Iodide; D002794:Choline; D000109:Acetylcholine; D002118:Calcium