Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors

Rathouz, Margaret; Vijayaraghavan, Sukumar; Berg, Daniela

doi:10.1007/bf02740649

Cited by 69 publications

(42 citation statements)

References 107 publications

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“…The most likely candidates, based on their relatively high conductance through the channel (Rathouz et al, 1996;Burnashev, 1998), are sodium (which could cause a local depolarisation) and calcium. It was important to explore the possibility that local depolarisation and subsequent ¢ring of action potentials could occur as it has been previously reported that nicotine can elicit antidromic nerve action potentials in cardiac sympathetic nerve terminals (Bevan and Haeusler, 1975).…”

Section: Discussionmentioning

confidence: 99%

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

et al. 2001

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AbstractöWhile nicotine is known to act at neuronal nicotinic acetylcholine receptors (nAChRs) to facilitate neurotransmitter release, the mechanisms underlying this action are poorly understood. Some of its e¡ects are known to be mediated by presynaptic receptors. In the mouse vas deferens nicotine (10^30 WM) transiently increased the force of neurogenic contraction by 135 þ 25%, increased the amplitude of excitatory junction potentials by 74 þ 6% and increased the frequency of spontaneous excitatory junction potentials in four out of six preparations. Confocal microscopy and the calcium indicator Oregon Green 488 BAPTA-1 dextran were used to measure calcium concentration changes in the nerve terminals. Nicotine did not a¡ect the action potential-evoked calcium transient but instead triggered small, random £uctuations (`calcium spikes') in intra-varicosity calcium concentrations at an average frequency of 0.09 þ 0.02 Hz. These were insensitive to tetrodotoxin at a concentration that blocked action-potential evoked calcium transients (300 nM). They were abolished by the nAChR blocker hexamethonium (100 WM) and by both ryanodine (100 WM) and ca¡eine (3 mM), agents that modify calcium release from intracellular stores.We propose a novel mechanism whereby nicotine's action at nAChRs triggers calcium-induced calcium release from a ryanodine-sensitive calcium store in nerve terminals. This primes neurotransmitter release mechanisms and enhances both spontaneous and action potential-evoked neurotransmitter release. ß

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Section: Discussionmentioning

confidence: 99%

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

et al. 2001

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“…9). Because the ␣7* subtype is the most highly permeable nAChR to calcium, it often mediates a direct Ca 2+ increase as well as initiating indirect Ca 2+ influx caused by the local depolarization and via intracellular Ca 2+ stores (Séguéla et al 1993;Gray et al 1996;Rathouz et al 1996;Radcliffe and Dani 1998;McGehee 2000, 2002;Ji et al 2001;. Consequently, the activation of presynaptic ␣7* nAChRs initiates a calcium increase in the glutamatergic presynaptic terminals that increases glutamate release and excitation of DA neurons, even while the ␤2* nAChRs on the DA neurons are desensitizing (see Fig.…”

Section: Learning and Memory 65mentioning

confidence: 99%

Nicotinic Cholinergic Synaptic Mechanisms in the Ventral Tegmental Area Contribute to Nicotine Addiction

Pidoplichko¹,

Noguchi²,

Areola³

et al. 2004

Learn. Mem.

172

158

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Tobacco use is a major health problem that is estimated to cause 4 million deaths a year worldwide. Nicotine is the main addictive component of tobacco. It acts as an agonist to activate and desensitize nicotinic acetylcholine receptors (nAChRs). A component of nicotine's addictive power is attributable to actions on the mesolimbic dopaminergic system, which serves a fundamental role in the acquisition of behaviors that are inappropriately reinforced by addictive drugs. Here we show that nicotine, in the same concentration and time ranges as obtained from tobacco, has three main actions that regulate the activity of midbrain dopamine (DA) neurons. Nicotine first activates and then desensitizes nAChRs on the DA neurons. This process directly excites the DA neurons for a short period of time before the nAChRs desensitize. Nicotine also enhances glutamatergic excitation and decreases GABAergic inhibition onto DA neurons. These events increase the probability for synaptic plasticity, such as long-term potentiation. The short-lived direct excitation of the DA neurons coupled with the enhanced glutamatergic afferent activity provides the presynaptic and postsynaptic coincidence necessary to initiate synaptic potentiation. In total, these synaptic events lead to a relatively long-lasting heightened activity of midbrain DA neurons. Consistent with other summarized studies, this work indicates that the synaptic changes normally associated with learning and memory can be influenced and commandeered during the nicotine addiction process.

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“…Both are known to contribute to calcium levels in the neurons (Rathouz et al, 1996;Brain and Bennett, 1998). L-type calcium channels are distributed all over the cell body, as revealed by immunostaining with a monoclonal antibody directed against the ␣ 1c subunit; no preferential localization is seen on spine mats defined by staining for ␣7-nAChRs (Fig.…”

Section: Sustained Calcium Increases Depend On Multiple Calcium Sourcesmentioning

confidence: 99%

Synaptically Driven Calcium Transients via Nicotinic Receptors on Somatic Spines

Shoop

Chang²,

Ellisman

et al. 2001

J. Neurosci.

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Dendritic spines commonly receive glutamatergic innervation at postsynaptic densities and compartmentalize calcium influx arising from synaptic signaling. Recently, it was shown that a class of nicotinic acetylcholine receptors containing ␣7 subunits is concentrated on somatic spines emanating from chick ciliary ganglion neurons. The receptors have a high relative calcium permeability and contribute importantly to synaptic currents, although they appear to be excluded from postsynaptic densities. Here we show that low-frequency synaptic stimulation of the ␣7-containing receptors induces calcium transients confined to the spines. Highfrequency stimulation induces a transient calcium elevation in the spines and a more sustained cell-wide elevation. The highfrequency transient elevation again depends on ␣7-containing receptors, whereas the sustained elevation can be triggered by other nicotinic receptors and depends on calcium release from internal stores and probably influx through voltage-gated L-type calcium channels as well. Retrograde axonal stimulation of the neurons at high frequency mimics synaptic stimulation in producing sustained cell-wide calcium increases that depend on L-type channels and release from internal stores, but it does not produce calcium transients in the spines. Thus frequent action potentials are sufficient to generate the cell-wide increases, but ␣7-containing receptors are needed for spine-specific effects. Patchclamp recording indicates that ␣7-containing receptors preferentially desensitize at high-frequency stimulation, accounting for the inability of the stimulation to sustain high calcium levels in the spines. The spatial and temporal differences in the patterns of calcium elevation could enable the neurons to monitor their own firing histories for regulatory purposes.

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Elevation of intracellular calcium levels in neurons by nicotinic acetylcholine receptors

Cited by 69 publications

References 107 publications

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

Nicotinic Cholinergic Synaptic Mechanisms in the Ventral Tegmental Area Contribute to Nicotine Addiction

Synaptically Driven Calcium Transients via Nicotinic Receptors on Somatic Spines

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