Nicotinic acetylcholine receptors in mouse and rat optic nerves.
Receptor-mediated calcium signaling in axons of mouse and rat optic nerves was examined by selectively staining the axonal population with a calcium indicator. Nicotine (1-50 microM) induced an axonal calcium elevation that was eliminated when calcium was removed from the bath, suggesting that nicotine induces calcium influx into axons. The nicotine response was blocked by d-tubocurarine and mecamylamine but not alpha-bungarotoxin, indicating the presence of calcium permeable, non-alpha7 nicotinic acetylcholine receptor (nAChR) subtype. Agonist efficacy order for eliciting the axonal nAChR calcium response was cytisine approximately nicotine >> acetylcholine. The nicotine-mediated calcium response was attenuated during the process of normal myelination, decreasing by approximately 10-fold from P1 (premyelinated) to P30 (myelinated). Nicotine also caused a rapid reduction in the compound action potential in neonatal optic nerves, consistent with a shunting of the membrane after opening of the nonspecific cationic nicotinic channels. Voltagegated calcium channels contributed little to the axonal calcium elevation during nAChR activation. During repetitive stimulations, the compound action potential in neonatal mouse optic nerves underwent a gradual reduction in amplitude that could be partially prevented by d-tubocurarine, suggesting an activity-dependent release of acetylcholine that activates axonal AChRs. We conclude that mammalian optic nerve axons express nAChRs and suggest that these receptors are activated in an activity-dependent fashion during optic nerve development to modulate axon excitability and biology.
Zhang
Chuan-Li
CL
Department of Physiology, University of Wisconsin School of Medicine, Madison, Wisconsin 53706, USA.
Verbny
Yakov
Y
Malek
Sameh A
SA
Stys
Peter K
PK
Chiu
Shing Yan
SY
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D009900:Optic Nerve / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*
D011978:Receptors, Nicotinic; D009538:Nicotine