Synaptic-type acetylcholine receptors raise intracellular calcium levels in neurons by two mechanisms

Rathouz, Margaret; Berg, Daniela

doi:10.1523/jneurosci.14-11-06935.1994

Cited by 112 publications

(93 citation statements)

References 56 publications

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“…There are three types of cytoplasmic calcium signals initiated by neuronal nAChR activation; (1) direct calcium influx through the nAChR [6,11] , (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization [6,11] , and (3) calcium-induced calcium release (CICR) (triggered by the two sources listed above) from the endoplasmic reticulum (ER) through the ryanodine receptors [12][13][14] and inositol (1,4,5)-triphosphate receptors (IP 3 Rs) [13][14][15] .…”

Section: Cytoplasmic Calcium Signals Initiated By Neuronal Nachr Actimentioning

confidence: 99%

“…The nAChRs that contain α3 and/or β2 subunits in brain and ganglionic neuronal preparations are associated predominantly with calcium signals that are mediated by depolarization and the activation of VDCCs [12,14,24] , as well as the α7 nAChRs [25,26] . Calcium influx through VDCCs augments the primary calcium signals generated by the direct influx through nAChRs [11,14] . These two mechanisms may be physiologically complementary; calcium entry through inwardly rectifying nAChRs will be robust under either resting or hyperpolarized potentials, whereas calcium influx through VDCCs will occur mainly at more depolarized potentials (-40 mV) [27] .…”

Section: Cytoplasmic Calcium Signals Initiated By Neuronal Nachr Actimentioning

confidence: 99%

“…Both the direct calcium influx through nAChRs, and indirect calcium influx through VDCCs, can then trigger calcium release from intracellular calcium stores as noted above [6] . In chick ciliary ganglion neurons, a major portion of the nAChR-induced changes in cytoplasmic calcium levels is due to influx through VDCCs [11,26] . In cultured hippocampal neurons, about 85% of the nAChR-mediated calcium level changes were blocked by cadmium, a VDCC blocker, suggesting that most of the calcium influx was through VDCCs [25] .…”

Section: Instantaneous Effectsmentioning

confidence: 99%

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Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

2009

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Based on the composition of the five sub units forming functional neuronal nicotinic acetylcholine receptors (nAChRs), they are grouped into either heteromeric (comprising both α and β subunits) or homomeric (comprising only α subunits) receptors. The nAChRs are known to be differentially permeable to calcium ions, with the α7 nAChR subtype having one of the highest permeabilities to calcium. Calcium influx through nAChRs, particularly through the α-bungarotoxin-sensitive α7-containing nAChRs, is a very efficient way to raise cytoplasmic calcium levels. The activation of nAChRs can mediate three types of cytoplasmic calcium signals: (1) direct calcium influx through the nAChRs, (2) indirect calcium influx through voltage-dependent calcium channels (VDCCs) which are activated by the nAChR-mediated depolarization, and (3) calciuminduced calcium release (CICR) (triggered by the first two sources) from the endoplasmic reticulum (ER) through the ryanodine receptors and inositol (1,4,5)-triphosphate receptors (IP 3 Rs). Downstream signaling events mediated by nAChRmediated calcium responses can be grouped into instantaneous effects (such as neurotransmitter release, which can occur in milliseconds after nAChR activation), short-term effects (such as the recovery of nAChR desensitization through cellular signaling cascades), and long-term effects (such as neuroprotection via gene expression). In addition, nAChR activity can be regulated by cytoplasmic calcium levels, suggesting a complex reciprocal relationship. Further advances in imaging techniques, animal models, and more potent and subtype-selective ligands for neuronal nAChRs would help in understanding the neuronal nAChR-mediated calcium signaling, and lead to the development of improved therapeutic treatments.

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Section: Cytoplasmic Calcium Signals Initiated By Neuronal Nachr Actimentioning

confidence: 99%

Section: Cytoplasmic Calcium Signals Initiated By Neuronal Nachr Actimentioning

confidence: 99%

Section: Instantaneous Effectsmentioning

confidence: 99%

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Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

2009

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“…The P Ca /P Na ratios calculated for nAChRs range from about 1 for ganglionic nAChRs (Fieber and Adams, 1991;Rathouz and Berg, 1994) to about 20 for heterologously expressed ␣7 gene product (Seguela et al, 1993). The ␣Bgt-sensitive current from cultured hippocampal neurons exhibit a P Ca /P Na ratio of 5 (Castro and Albuquerque, 1995).…”

Section: Calcium Flux Through Nachrsmentioning

confidence: 99%

“…This is clearly a dominant mechanism in neurons. In chick ciliary ganglion neurons, a major portion of nAChR-induced changes in bulk calcium is due to influx through VGCCs (Vijayaraghavan et al, 1992;Rathouz and Berg, 1994). In cultured hippocampal neurons, about 85% of nAChR-mediated bulk calcium changes were blocked by cadmium, suggesting that most of the calcium flux was through VGCCs (Barrantes et al, 1995).…”

Section: Calcium Flux Through Nachrsmentioning

confidence: 99%

Nicotinic receptor signaling in nonexcitable cells

2002

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ABSTRACT:The finding that neuronal nicotinic acetylcholine receptors (nAChRs) are present in nonneuronal cells both within and outside the nervous system raises some interesting issues. The mechanisms underlying receptor signaling and its downstream consequences in these cells remain to be elucidated. Factors controlling the release of acetylcholine and the extent of its diffusion are likely to be different for these cells than for traditional neuronal synapses. Recent advances on the physiologic functions of some of these cell types have provided a better insight into possible functional roles for nAChRs in nonexcitable cells. The presence of nAChRs on these cells also implies a broader scope for the actions of nicotine that needs to be considered from a clinical viewpoint. Revealing the potential physiologic roles for nAChRs on nonexcitable cells is likely to provide a more complete understanding of cholinergic signaling.

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Neuromuscular development in the avian paralytic mutant crooked neck dwarf (cn/cn): further evidence for the role of neuromuscular activity in motoneuron survival

et al. 1997

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Neuromuscular transmission and muscle activity during early stages of embryonic development are known to influence the differentiation and survival of motoneurons and to affect interactions with their muscle targets. We have examined neuromuscular development in an avian genetic mutant, crooked neck dwarf (cn/cn), in which a major phenotype is the chronic absence of the spontaneous, neurally mediated movements (motility) that are characteristic of avian and other vertebrate embryos and fetuses. The primary genetic defect in cn/cn embryos responsible for the absence of motility appears to be the lack of excitation-contraction coupling. Although motility in mutant embryos is absent from the onset of activity on embryonic days (E) 3-4, muscle differentiation appears histologically normal up to about E8. After E8, however, previously separate muscles fuse or coalesce secondarily, and myotubes exhibit a progressive series of histological and ultrastructural degenerative changes, including disarrayed myofibrils, dilated sarcoplasmic vesicles, nuclear membrane blebbing, mitochondrial swelling, nuclear inclusions, and absence of junctional end feet. Mutant muscle cells do not develop beyond the myotube stage, and by E18-E20 most muscles have almost completely degenerated. Prior to their breakdown and degeneration, mutant muscles are innervated and synaptic contacts are established. In fact, quantitative analysis indicates that, prior to the onset of muscle degeneration, mutant muscles are hyperinnervated. There is increased branching of motoneuron axons and an increased number of synaptic contacts in the mutant muscle on E8. Naturally occurring cell death of limb-innervating motoneurons is also significantly reduced in cn/cn embryos. Mutant embryos have 30-40% more motoneurons in the brachial and lumbar spinal cord by the end of the normal period of cell death. Electrophysiological recordings (electromyographic and direct records form muscle nerves) failed to detect any differences in the activity of control vs. mutant embryos despite the absence of muscular contractile activity in the mutant embryos. The alpha-ryanodine receptor that is genetically abnormal in homozygote cn/cn embryos is not normally expressed in the spinal cord. Taken together, these data argue against the possibility that the mutant phenotype described here is caused by the perturbation of a central nervous system (CNS)-expressed alpha-ryanodine receptor. The hyperinnervation of skeletal muscle and the reduction of motoneuron death that are observed in cn/cn embryos also occur in genetically paralyzed mouse embryos and in pharmacologically paralyzed avian and rat embryos. Because a primary common feature in all three of these models is the absence of muscle activity, it seems likely that the peripheral excitation of muscle by motoneurons during normal development is a major factor in regulating retrograde muscle-derived (or muscle-associated) signals that control motoneuron differentiation and survival.

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Synaptic-type acetylcholine receptors raise intracellular calcium levels in neurons by two mechanisms

Cited by 112 publications

References 56 publications

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

Nicotinic receptor signaling in nonexcitable cells

Neuromuscular development in the avian paralytic mutant crooked neck dwarf (cn/cn): further evidence for the role of neuromuscular activity in motoneuron survival

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