Physiological Roles of Neuronal Nicotinic Receptors Subtypes: New Insights on the Nicotinic Modulation of Neurotransmitter Release, Synaptic Transmission and Plasticity

Sher, Emanuele; Chen, Y.; Sharples, Thomas J.W.; Broad, Lisa M.; Benedetti, Giovanni; Zwart, Ruud; McPhie, Gordon; Pearson, Kathy H.; Baldwinson, Tristan; Filippi, Giovanna De

doi:10.2174/1568026043451393

Cited by 94 publications

(83 citation statements)

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“…In the central nervous system, ␣4␤2 nACh receptors are located both pre-and postsynaptically and play an important modulatory role in synaptic transmission (Sher et al, 2004;Dani and Bertrand, 2007). Because AEA acts at the nAChR at physiologically relevant concentrations (Oz, 2006) and given the presence of ␣4␤2 nACh receptors in these critical locations, it is possible that the activity of the ␣4␤2 nACh receptor function is regulated by both tonic and phasic AEA in situ.…”

Section: Discussionmentioning

confidence: 99%

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

Spivak¹,

Lupica²,

Öz³

2007

Mol Pharmacol

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The effects of the endocannabinoid anandamide (arachidonylethanolamide, AEA) on the function of ␣4␤2 nicotinic acetylcholine receptors (nAChR) stably expressed in SH-EP1 cells were investigated using the whole-cell patch-clamp technique. In the concentration range of 200 nM to 2 M, AEA significantly reduced the maximal amplitudes and increased the desensitization of acetylcholine (ACh)-induced currents. The effects of AEA could be neither replicated by the exogenous cannabinoidThe actions of AEA were apparent when applied extracellularly but not during intracellular dialysis. Furthermore, the effects of AEA ACh currents were not altered by the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid. The onset and washout of the AEA effects required several minutes (10 -30 min), but the latter was significantly decreased in the presence of lipid-free bovine serum albumin (BSA). Moreover, BSA alone increased peak ACh current amplitudes and diminished desensitization rates in naive cells, suggesting a tonic modulation of ␣4␤2 nAChR function by an endogenous AEA-like lipid. Further analysis of AEA effects on ␣4␤2 nAChR-mediated currents, using a twostage desensitization model, indicated that the first forward rate constant leading to desensitization, k 1 , increased nearly 30-fold as a linear function of the AEA concentration. In contrast, the observation that the other three rate constants were unaltered by AEA suggested that AEA raised the energy of the activated state. These results indicate that AEA directly inhibits the function of ␣4␤2 nAChRs in a CB1 receptor-independent manner.

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Section: Discussionmentioning

confidence: 99%

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

Spivak¹,

Lupica²,

Öz³

2007

Mol Pharmacol

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“…However, it is known that homologous ␣7 and heterologous ␣4␤2 nAChRs are more commonly expressed in the CNS (Whiting et al, 1987;Flores et al, 1992;Séguéla et al, 1993). Several studies have demonstrated that neuronal nAChRs have a preferential presynaptic location and act to increase the release of a large number of neurotransmitters (Wonnacott, 1997;Sher et al, 2004;Jensen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Presynaptic α4β2 Nicotinic Acetylcholine Receptors Increase Glutamate Release and Serotonin Neuron Excitability in the Dorsal Raphe Nucleus

Garduño¹,

Galindo-Charles²,

Jiménez-Rodríguez³

et al. 2012

J. Neurosci.

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Several behavioral effects of nicotine are mediated by changes in serotonin (5-HT) release in brain areas that receive serotonergic afferents from the dorsal raphe nucleus (DRN). In vitro experiments have demonstrated that nicotine increases the firing activity in the majority of DRN 5-HT neurons and that DRN contains nicotinic acetylcholine receptors (nAChRs) located at both somata and presynaptic elements. One of the most common presynaptic effects of nicotine is to increase glutamate release. Although DRN receives profuse glutamatergic afferents, the effect of nicotine on glutamate release in the DRN has not been studied in detail. Using whole-cell recording techniques, we investigated the effects of nicotine on the glutamatergic input to 5-HT DRN neurons in rat midbrain slices. Low nicotine concentrations, in the presence of bicuculline and tetrodotoxin (TTX), increased the frequency but did not change the amplitude of glutamate-induced EPSCs, recorded from identified 5-HT neurons. Nicotine-induced increase of glutamatergic EPSC frequency persisted 10 -20 min after drug withdrawal. This nicotinic effect was mimicked by exogenous administration of acetylcholine (ACh) or inhibition of ACh metabolism. In addition, the nicotine-induced increase in EPSC frequency was abolished by blockade of ␣4␤2 nAChRs, voltagegated calcium channels, or intracellular calcium signaling but not by ␣7 nAChR antagonists. These data suggest that both nicotine and endogenous ACh can increase glutamate release through activation of presynaptic ␣4␤2 but not ␣7 nAChRs in the DRN. The effect involves long-term changes in synaptic function, and it is dependent on voltage-gated calcium channels and presynaptic calcium stores.

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“…That nAChR signaling is crucial for these behaviors has been confirmed by recent studies on animals carrying gain-of-function or loss-offunction mutations in neuronal nAChR subunit genes (CorderoErausquin et al, 2000;Picciotto et al, 2001;Wang et al, 2002;Tapper et al, 2004;Maskos et al, 2005). How neuronal nAChRs alter the function of neural circuits depends primarily on where the receptors are located: on some neurons, such as those in peripheral sympathetic ganglia, nAChRs are targeted to the soma-dendritic domain where they mediate fast excitatory synaptic transmission (De Biasi, 2002: Skok, 2002); on other neurons, particularly those in the CNS, nAChRs are targeted to preterminal axons or presynaptic terminals where they modify GABA or glutamate transmitter release (Gray et al, 1996;Role and Berg, 1996;Broide and Leslie, 1999;MacDermott et al, 1999;Sher et al, 2004;Gotti et al, 2006). Because of the difficulties in recording directly from nAChRs on nerve terminals, however, we know little about the precise manner by which nAChR-mediated depolarizations modulate presynaptic transmitter release.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

Campanucci¹,

Krishnaswamy²,

Cooper³

2008

J. Neurosci.

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Neuronal nicotinic acetylcholine receptors (nAChRs), ligand-gated ion channels implicated in a variety of cognitive, motor, and sensory behaviours, are targeted to compartments rich in mitochondria, particularly postsynaptic domains and presynaptic terminals, exposing these receptors to reactive oxygen species (ROS) generated by oxidative phosphorylation. In addition, these receptors can become exposed to ROS during the progression of certain neurodegenerative diseases. Because ROS are known to modify several membrane proteins, including some types of ion channels, it raises the question of whether elevations in cytosolic ROS alter the function of nAChRs. To address this, we elevated ROS in cultured sympathetic neurons, directly by perfusing neurons intracellularly with ROS, indirectly by blocking the mitochondrial electron transport chain, or noninvasively by transient NGF removal; we then simultaneously measured changes in cytosolic ROS levels and whole-cell ACh-evoked currents. In addition, we elevated cytosolic ROS in postganglionic neurons in intact ganglia and measured changes in nerve-evoked EPSPs. Our experiments indicate that mild elevations in cytosolic ROS, including that produced by transient interruption of NGF signaling, induce a use-dependent, long-lasting rundown of ACh-evoked currents on cultured sympathetic neurons and a long-lasting depression of fast nerve-evoked EPSPs. We show that these effects of cytosolic ROS are specific to nAChRs on neurons and do not cause rundown of ACh-evoked currents on muscle. Our results demonstrate that elevations in cytosolic ROS inactivate neuronal nAChRs in a use-dependent manner and suggest that mild oxidative stress impairs mechanisms mediated by cholinergic nicotinic signaling at neuronal-neuronal synapses.

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Physiological Roles of Neuronal Nicotinic Receptors Subtypes: New Insights on the Nicotinic Modulation of Neurotransmitter Release, Synaptic Transmission and Plasticity

Cited by 94 publications

References 0 publications

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

The Endocannabinoid Anandamide Inhibits the Function of α4β2 Nicotinic Acetylcholine Receptors

Presynaptic α4β2 Nicotinic Acetylcholine Receptors Increase Glutamate Release and Serotonin Neuron Excitability in the Dorsal Raphe Nucleus

Mitochondrial Reactive Oxygen Species Inactivate Neuronal Nicotinic Acetylcholine Receptors and Induce Long-Term Depression of Fast Nicotinic Synaptic Transmission

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