5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calciumm-induced calcium release

Rondé, Philippe; Nichols, Robert A.

doi:10.1016/s0143-4160(97)90020-8

Cited by 36 publications

(25 citation statements)

References 38 publications

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“…i by 5-HT up-regulated in differentiated NG cells is almost all because of the activation of the 5-HT 3 receptor. NG cells express 5-HT 3 receptors as reported previously [11,12,15]. On the other hand, we have also reported that the enhancement of TTX-sensitive Na ?…”

Section: Discussionsupporting

confidence: 88%

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Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

et al. 2008

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Characteristics for the up-regulated response in the concentration of intracellular calcium ion ([Ca(2+)]( i )) and in the sodium ion (Na(+)) current by serotonin (5-HT) were investigated in differentiated neuroblastoma x glioma hybrid NG108-15 (NG) cells. The results for the changes in [Ca(2+)]( i ) by 5-HT were as follows, (1) The 5-HT-induced Ca(2+) response was inhibited by 3 x 10(-9) M tropisetron (a 5-HT(3) receptor blocker), but not by other types of 5-HT receptor blockers; (2) The 5-HT-induced Ca(2+) response was mainly inhibited by calciseptine (a L-type Ca(2+) blocker), but not by other types of Ca(2+) channel blockers or 10(-7) M TTX (a voltage-sensitive Na(+) channel blocker); (3) When the extracellular Na(+) was removed by exchange with choline chloride or N-methyl-D-glucamine, the 5-HT-induced Ca(2+) response was extremely inhibited. The results for the 5-HT-induced Na(+) current by the whole cell patch-clamp technique were as follows, (1) The 5-HT-induced Na(+) current in differentiated cells was significantly larger than that in undifferentiated cells; (2) The ED(50) value for 5-HT-induced Na(+) current in undifferentiated and differentiated cells was almost the same, about 4 x 10(-6) M each other; (3) The 5-HT-induced Na(+) current was completely blocked by 3 x 10(-9) M tropisetron, but not by other 5-HT receptor antagonists and 10(-7) M TTX. These results suggested that 5-HT-induced Ca(2+) response in differentiated NG cells was mainly due to L-type voltage-gated Ca(2+) channels allowing extracellular Na(+) to enter via 5-HT(3) receptors, but not through voltage-gated Na(+) channels.

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Section: Discussionsupporting

confidence: 88%

“…It is well known that an activation of the 5-HT 3 receptor induces an increase in [Ca 2? ] i via L-type VGCCs in a few types of neuronal cells [11,12,15]. Peter et al [16] have reported that the inward current elicited by an activation of 5-HT 3 receptors is mainly due to an increase of conductance for Na ?…”

Section: Discussionmentioning

confidence: 99%

Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

et al. 2008

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“…Because patch-clamp analysis is time consuming and requires specialized technical equipment and expertise for the characterization of multiple ion channel isoforms, we have established an alternative technique for fast and effective functional analysis of the 5-HT 3 subunit candidates: the aequorin assay. Based on the calcium permeability of the 5-HT 3 receptor (Hargreaves et al, 1994;Rondé and Nichols, 1997;Davies et al, 1999), agonist stimulation induces a concentration-dependent influx of calcium ions through the open-channel pore, which leads to aequorin bio- For each subunit combination, three to five independent experiments were performed in triplicate. Nonspecific binding in the presence of 100 M MDL72222 was approximately 10% of overall binding.…”

Section: Resultsmentioning

confidence: 99%

Characterization of the Novel Human Serotonin Receptor Subunits 5-HT_3C,5-HT_3D, and 5-HT_3E

Niesler¹,

Walstab²,

Combrink³

et al. 2007

Mol Pharmacol

149

139

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Within the family of serotonin receptors, the 5-hydroxytryptamine-3 (5-HT 3 ) receptor is the only ligand-gated ion channel. It is composed of five subunits, of which the 5-HT 3A and 5-HT 3B subunits are best characterized. Several studies, however, have reported on the functional diversity of native 5-HT 3 receptors, which cannot solely be explained on the basis of the 5-HT 3A and 5-HT 3B subunits. After our discovery of further putative 5-HT 3 serotonin receptor-encoding genes, HTR3C, HTR3D, and HTR3E, we investigated whether these novel candidates and the isoform 5-HT 3Ea are able to form functional 5-HT 3 receptor complexes. Using immunofluorescence and immunoprecipitation studies of heterologously expressed proteins, we found that each of the respective candidates coassembles with 5-HT 3A . To investigate whether the novel subunits modulate 5-HT 3 receptor function, we performed radioligandbinding assays and calcium-influx studies in human embryonic kidney 293 cells. Our experiments revealed that the 5-HT 3C , 5-HT 3D , 5-HT 3E , and 5-HT 3Ea subunits alone cannot form functional receptors. Coexpression with 5-HT 3A , however, results in the formation of functional heteromeric complexes with different serotonin efficacies. Potencies of two agonists and antagonists were nearly identical with respect to homomeric 5-HT 3A and heteromeric complexes. However, 5-HT showed increased efficacy with respect to 5-HT 3A/D and 5-HT 3A/E receptors, which is consistent with the increased surface expression compared with 5-HT 3A receptors. In contrast, 5-HT 3A/C and 5-HT 3A/Ea receptors exhibited decreased 5-HT efficacy. These data show for the first time that the novel 5-HT 3 subunits are able to form heteromeric 5-HT 3 receptors, which exhibit quantitatively different functional properties compared with homomeric 5-HT 3A receptors.The 5-HT 3 receptor is the only ligand-gated ion channel (LGIC) within the family of serotonin (5-hydroxytryptamine, 5-HT) receptors (Hoyer et al., 2002). Based on structural and functional homologies, the nicotinic acetylcholine receptor and the 5-HT 3 receptor are most closely related; both are cation channels. The 5-HT 3 receptor is formed by a pentameric complex and is permeable to Na ϩ , K ϩ , and Ca 2ϩ . Binding of serotonin to the 5-HT 3 receptor leads to a fast excitatory response of the neuron. After cloning of the human HTR3A gene (Belelli et al., 1995;Miyake et al., 1995), findings concerning variable receptor compositions and properties led to the hypothesis that further 5-HT 3 receptor subunits and isoforms should exist (Hussy et al., 1994;Jackson and Yakel, 1995;Fletcher and Barnes, 1998). This hypothesis was confirmed by the cloning of the human HTR3B gene (Davies et al., 1999) and of two different human splice variants of the HTR3A gene (Brü ss et al., 2000). To date, HTR3A and HTR3B (Belelli et al., 1995;Miyake et al., 1995;Davies et al., 1999) are well characterized. 5-HT 3A subunits are able to form functional homooligomeric receptors after expression in Xenopus laevi...

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“…The dihydropyridine agonist BayK-8644 did not enhance Ca 2ϩ influx in mature Purkinje neurons (Usowicz et al, 1992), implying that L-type Ca 2ϩ channels do not play a prominent functional role in the mature dendritic arbor. However, the N-type Ca 2ϩ channel blocker -conotoxin GVIA inhibited 6%, and the L-type Ca 2ϩ channel blocker nitrendipine inhibited 8% of the high-threshold Ca 2ϩ currents in acutely isolated Purkinje neurons from 1-to 3-week-old rats (Regan, 1991 (Hayashi et al, 1997) and agonist-evoked Ca 2ϩ signals in other neuronal types (Chavis et al, 1996;Ronde and Nichols, 1997 (Llano et al, 1994;Gruol et al, 1996). Future studies will address this issue.…”

Section: Discussionmentioning

confidence: 95%

L-Type Calcium Channels Mediate Calcium Oscillations in Early Postnatal Purkinje Neurons

2000

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Ca2ϩ signaling is important in many fundamental neuronal processes including neurotransmission, synaptic plasticity, neuronal development, and gene expression. In cerebellar Purkinje neurons, Ca 2ϩ signaling has been studied primarily in the dendritic region where increases in local Ca 2ϩ have been shown to occur with both synaptic events and spontaneous electrical activity involving P-type voltage-gated Ca 2ϩ channels (VGCCs), the predominant VGCC expressed by Purkinje neurons. Here we show that Ca 2ϩ signaling is also a prominent feature of immature Purkinje neurons at developmental stages that precede expression of dendritic structure and involves L-type rather than P-type VGCCs. Immature Purkinje neurons acutely dissociated from postnatal day 4-7 rat pups exhibit spontaneous cytoplasmic Ca 2ϩ oscillations. The Ca 2ϩ oscillations require entry of extracellular Ca 2ϩ , are blocked by tetrodotoxin, are communicated to the nucleus, and correlate closely with patterns of endogenously generated spontaneous and evoked electrical activity recorded in the neurons. Immunocytochemistry showed that L-, N-, and P/Q-types of VGCCs are present on the somata of the Purkinje neurons at this age. However, only the L-type VGCC antagonist nimodipine effectively antagonized the Ca 2ϩ oscillations; inhibitors of P/Q and N-type VGCCs were relatively ineffective.

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5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calciumm-induced calcium release

Cited by 36 publications

References 38 publications

Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

Characterization of the Novel Human Serotonin Receptor Subunits 5-HT_3C,5-HT_3D, and 5-HT_3E

L-Type Calcium Channels Mediate Calcium Oscillations in Early Postnatal Purkinje Neurons

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5-HT3 receptors induce rises in cytosolic and nuclear calcium in NG108-15 cells via calciumm-induced calcium release

Cited by 36 publications

References 38 publications

Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

Characteristics for Enhanced Response of Serotonin-Evoked Ion Dynamics in Differentiated NG108-15 Cells

Characterization of the Novel Human Serotonin Receptor Subunits 5-HT3C,5-HT3D, and 5-HT3E

L-Type Calcium Channels Mediate Calcium Oscillations in Early Postnatal Purkinje Neurons

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Characterization of the Novel Human Serotonin Receptor Subunits 5-HT_3C,5-HT_3D, and 5-HT_3E