Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free ca2+

Vijayaraghavan, Sukumar; Pugh, Phyllis C.; Zhang, Zhongwei; Rathouz, Margaret; Berg, Daniela

doi:10.1016/0896-6273(92)90301-s

Cited by 257 publications

(162 citation statements)

References 53 publications

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“…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] .…”

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: Instantaneous Effectsmentioning

confidence: 99%

Nicotinic acetylcholine receptor-mediated calcium signaling in the nervous system

2009

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“…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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“…When expressed in Xenopus oocytes [9,10] or mammalian cells [11] , these receptors are highly permeable to calcium ion [12][13][14] . The α7 nAChRs have been implicated in a wide range of physiological functions, including neurotransmitter release [15,16] , activation of second messengers, apoptosis and neuroprotection [17,18] .…”

Section: Introductionmentioning

confidence: 99%

Rat neuronal nicotinic acetylcholine receptors containing α7 subunit: pharmacological properties of ligand binding and function

et al. 2009

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Aim:To compare pharmacological properties of heterologously expressed homomeric α7 nicotinic acetylcholine receptors (α7 nAChRs) with those of native nAChRs containing α7 subunit (α7* nAChRs) in rat hippocampus and cerebral cortex. Methods: We established a stably transfected HEK-293 cell line that expresses homomeric rat α7 nAChRs. We studies ligand binding profiles and functional properties of nAChRs expressed in this cell line and native rat α7* nAChRs in rat hippocampus and cerebral cortex. We used [ 125 I]-α-bungarotoxin to compare ligand binding profiles in these cells with those in rat hippocampus and cerebral cortex. The functional properties of the α7 nAChRs expressed in this cell line were studied using whole-cell current recording. The acetylcholine activated currents were potently blocked by two selective antagonists of α7 nAChRs, α-bungarotoxin (IC 50 =19±2 nmol/L) and methyllycaconitine (IC 50 =100±10 pmol/L). A comparative study of ligand binding profiles, using 13 nicotinic ligands, showed many similarities between the homomeric α7 nAChRs and native α7* receptors in rat brain, but it also revealed several notable differences. Conclusion: This newly established stable cell line should be very useful for studying the properties of homomeric α7 nAChRs and comparing these properties to native α7* nAChRs.

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Nicotinic receptors that bind α-bungarotoxin on neurons raise intracellular free ca2+

Cited by 257 publications

References 53 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

Rat neuronal nicotinic acetylcholine receptors containing α7 subunit: pharmacological properties of ligand binding and function

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