Nicotinic Acetylcholine Receptors in Mouse and Rat Optic Nerves

2004 ◽  
Vol 91 (2) ◽  
pp. 1025-1035 ◽  
Author(s):  
Chuan-Li Zhang ◽  
Yakov Verbny ◽  
Sameh A. Malek ◽  
Peter K. Stys ◽  
Shing Yan Chiu
Keyword(s):  
Optic Nerve ◽  
Action Potential ◽  
Nicotinic Acetylcholine Receptors ◽  
Compound Action Potential ◽  
Calcium Response ◽  
Nicotinic Acetylcholine ◽  
Optic Nerves ◽  
Activity Dependent ◽  
Calcium Elevation ◽  
Compound Action

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 μM) 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 α-bungarotoxin, indicating the presence of calcium permeable, non-α7 nicotinic acetylcholine receptor (nAChR) subtype. Agonist efficacy order for eliciting the axonal nAChR calcium response was cytisine ∼ 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.

scholarly journals Axon Function Persists during Anoxia in Mammalian White Matter

2003 ◽  
Vol 23 (11) ◽  
pp. 1340-1347 ◽  
Author(s):  
Selva Baltan Tekkök ◽  
Angus M Brown ◽  
Bruce R Ransom
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Anaerobic Capacity ◽  
Compound Action Potential ◽  
Loss Of Function ◽  
Optic Nerves ◽  
Glucose Reduction ◽  
Matter Energy ◽  
Compound Action

Axon function in the CNS has been reported to fail rapidly during anoxia, implying that there is no anaerobic capacity. This phenomenon was reassessed in rodent white matter using mouse or rat optic nerve. Axon function was semiquantitatively measured as area under the compound action potential. Mouse optic nerves exposed to anoxia (30–180 minutes) or cyanide (30–60 minutes) at 37°C exhibited significant persistent function that was abolished by removing glucose. Reduction in compound action potential area increased with anoxia duration reaching a maximum of about 70% after 90 min. Rat optic nerves exposed to anoxia, in contrast to mouse optic nerves, showed rapid and complete loss of function. When artificial CSF glucose was increased from 10 to 30 mmol/L, rat optic nerves responded to anoxia in a similar manner to mouse optic nerves in 10-mmol/L glucose. The authors conclude that white matter is resistant to anoxia with a subset of axons able to subsist exclusively on anaerobically derived energy. Because the rat optic nerve is about twice the diameter of the mouse optic nerve, glucose diffusion into the rat optic nerve was inadequate during anoxia when artificial CSF glucose was 10 mmol/L but became adequate when artificial CSF glucose was 30 mmol/L. These observations have implications for white matter energy metabolism and susceptibility to injury during focal ischemia.

scholarly journals TRPA1 block protects against loss of white matter function during ischaemia in the mouse optic nerve

2021 ◽  
Author(s):  
Grace Flower ◽  
Vincenzo Giacco ◽  
Angela Roxas ◽  
Nicola B Hamilton-Whitaker ◽  
Andra Braban
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Neuronal Excitability ◽  
Glucose Deprivation ◽  
Compound Action Potential ◽  
Oxygen And Glucose Deprivation ◽  
Loss And Damage ◽  
Compound Action Potentials ◽  
Compound Action

Oligodendrocytes produce myelin which provides insulation to axons and speeds up neuronal transmission. In ischaemic conditions myelin is damaged, resulting to mental and physical disabilities. Therefore, it is important to understand how the functionality of oligodendrocytes and myelin is affected by ischaemia. Recent evidence suggests that oligodendrocyte damage during ischaemia is mediated by TRPA1, whose activation raises intracellular Ca2+ concentrations and damages compact myelin. Here, we show that TRPA1 is tonically active in oligodendrocytes and the optic nerve, as the specific TRPA1 antagonist, A-967079, decreases basal oligodendrocyte Ca2+ concentrations and increases the size of the compound action potential. Conversely, TRPA1 agonists reduce the size of the optic nerve compound action potential, and this effect is significantly reduced by the TRPA1 antagonist. These results indicate that glial TRPA1 regulates neuronal excitability in the white matter under physiological as well as pathological conditions. Importantly, we find that inhibition of TRPA1 prevents loss of compound action potentials during oxygen and glucose deprivation (OGD) and improves the recovery. TRPA1 block was effective when applied before, during or after OGD, indicating that the damage is occurring during ischaemia, but that therapeutic intervention is possible after the ischaemic insult. These results indicate that TRPA1 has an important role in the brain, and that its block may be effective in treating oligodendrocyte loss and damage in many white matter diseases.

scholarly journals Anoxia-Induced Changes in Extracellular K+ and pH in Mammalian Central White Matter

1992 ◽  
Vol 12 (4) ◽  
pp. 593-602 ◽  
Author(s):  
Bruce R. Ransom ◽  
Wolfgang Walz ◽  
Peter K. Davis ◽  
Walter G. Carlini
Keyword(s):  
White Matter ◽  
Optic Nerve ◽  
Action Potential ◽  
Glucose Concentration ◽  
Anaerobic Metabolism ◽  
Compound Action Potential ◽  
Average Maximum ◽  
Ionic Changes ◽  
Induced Changes ◽  
Compound Action

In gray matter (GM), anoxia induces prominent extracellular ionic changes that are important in understanding the pathophysiology of this insult. White matter (WM) is also injured by anoxia but the accompanying changes in extracellular ions have not been studied. To provide such information, the time course and magnitude of anoxia-induced changes in extracellular K+ concentration ([K+]o) and extracellular pH (pHo) were measured in the isolated rat optic nerve, a representative central WM tract, using ion-selective microelectrodes. Anoxia produced less extreme changes in [K+]o and pHo in WM than are known to occur in GM; in WM during anoxia, the average maximum [K+]o was 14 ± 2.9 m M (bath [K+]o = 3 m M) and the average maximum acid shift was 0.31 ± 0.07 pH unit. The extracellular space volume rapidly decreased by ∼20% during anoxia. Excitability of the rat optic nerve, monitored as the amplitude of the supramaximal compound action potential, was lost in close temporal association with the increase in [K+]o Increasing the bath glucose concentration from 10 to 20 m M resulted in a much larger acid shift during anoxia (0.58 ± 0.08 pH unit) and a smaller average increase in [K+]o (9.2 ± 2.6 m M). The increased extracellular glucose concentration presumably provided more substrate for anaerobic metabolism, resulting in more extracellular lactate accumulation (although not directly measured) and a greater acid shift. Enhanced anaerobic metabolism during anoxia would provide energy for operation of ion pumps, including the sodium pump, that would result in smaller changes in [K+]o. These effects were probably responsible for the observation that the optic nerve showed significantly less damage after 60 min of anoxia in the presence of 20 m M glucose compared to 10 m M glucose. Under normoxic conditions, increasing bath K+ concentration to 30 m M (i.e., well beyond the level shown to occur with anoxia) for 60 min caused abrupt loss of excitability during the period of application but minimal change in the amplitude of the compound action potential following the period of exposure. The anoxia-induced increase in [K+]o, therefore, was not itself directly responsible for irreversible loss of optic nerve function. These observations indicate that major qualitative differences exist between mammalian GM and WM with regard to anoxia-induced extracellular ionic changes.

Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats

2006 ◽  
Vol 1067 (1) ◽  
pp. 78-84 ◽  
Author(s):  
Manuel Roncagliolo ◽  
Carol Schlageter ◽  
Claudia León ◽  
Eduardo Couve ◽  
Christian Bonansco ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Action Potential ◽  
Compound Action Potential ◽  
Developmental Impairment ◽  
Compound Action
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