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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many synaptic connections are rejected during development, and the remainder are stabilized. Whether neuronal activity is important in this remodeling remains unknown. Cholinergic synapses are formed in tissue culture between the hybrid NG108-15 (neuroblastoma X glioma) cell and skeletal myotubes. We have investigated changes in these synapses brought about by chronic depolarization. Most myotubes are innervated under control conditions and recording from a myotube while stimulating a neighboring hybrid cell demonstrates that most hybrid-myotube pairs in anatomical proximity also are connected synaptically. Multiple innervation of one myotube by several hybrid cells is common. After 24 to 72 hr of cell depolarization with low concentrations of veratridine, myotubes continue to evidence synaptic activity, but the chance of evoking activity, in a given myotube by stimulation of a neighboring hybrid cell, is diminished to 30% of control values; only 5% of myotubes can be demonstrated to still have multiple innervation. However, the efficacy of synapses that persists after veratridine exposure is comparable to control. By 24 hr after removal of veratridine, synapse number returns to control levels. Tetrodotoxin prevents these effects. We suggest that components responsible for the well known development change from polyneuronal to mononeuronal innervation may be present and accessible to manipulation in this relatively well defined tissue culture system.
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PMID:Depolarization-induced synaptic plasticity at cholinergic synapses in tissue culture. 728 71

The potassium channel blocker, 4-aminopyridine (4-AP), stimulates neurotransmitter release via plasma membrane depolarization and subsequent activation of voltage-gated calcium channels. The present study assessed the effects of 4-AP on intracellular calcium levels in the human neuroblastoma cell line CHP-100. Blockade of K+ channels with 4-AP significantly increased intracellular calcium concentration ([Ca2+]i). This increase occurred via activation of plasma membrane Ca2+ channels. The 4-AP induced rise in [Ca2+]i was not inhibited by the L-type Ca2+ channel blocker nifedipine but was sensitive to the N-type Ca2+ channel blocker omega-contotoxin GVIA. Tetrodotoxin did not alter the effect of 4-AP. These results suggest that in CHP-100 cells, following inhibition of K+ channels by 4-AP, N-type Ca2+ channels are activated.
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PMID:Inhibition of K+ channel activity by 4-AP stimulates N-type Ca2+ channels in CHP-100 cells. 791 77

Measurement of intracellular Ca2+ concentration ([Ca2+]i) in cultured mouse NG108-15 neuroblastoma x glioma hybrid cells, using the fluorescent probe fura-2, revealed that 5-25 nM ciguatoxin (CTX) increased [Ca2+]i either in cells bathed in standard medium or after removal of external Ca2+ by a Ca(2+)-free medium supplemented with EGTA. Tetrodotoxin prevented the CTX increased [Ca2+]i suggesting that CTX-induced mobilization of intracellular Ca2+ depends on Na+ influx through voltage-gated Na channels. CTX-induced Ca2+ mobilization prevented subsequent action of bradykinin (1 microM) suggesting that CTX stimulates the inositol 1,4,5-trisphosphate-releasable Ca2+ store.
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PMID:Ciguatoxin, extracted from poisonous morays eels, causes sodium-dependent calcium mobilization in NG108-15 neuroblastoma x glioma hybrid cells. 823 88

Na+ flux was studied in cultured neuroblastoma cells grown in medium containing increased glucose or L-fucose concentrations. Chronic exposure of neuroblastoma cells to 30 mM glucose or 30 mM L-fucose caused a decrease in ouabain-sensitive and veratridine-stimulated 22Na+ uptake compared with cells cultured in unsupplemented medium. The Na+ current, determined by using whole-cell configuration of the patch clamp, was also decreased in these cells. Tetrodotoxin (3 microM), which blocked whole cell Na+ currents, also blocked veratridine-stimulated 22Na+ accumulation. Culturing cells in medium containing 30 mM fructose as an osmotic control had no effect on Na+ flux. Specific [3H]saxitoxin binding was not affected by 30 mM glucose or 30 mM L-fucose compared with cells grown in unsupplemented medium, suggesting that the number of Na+ channels was not decreased. These studies suggest that exposing cultured neuronal cells to conditions that occur in the diabetic milieu alters Na+ transport and Na(+)-channel activity.
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PMID:Elevated levels of glucose and L-fucose reduce 22Na+ uptake and whole cell Na+ current in cultured neuroblastoma cells. 826 45

To examine the molecular basis for membrane excitability in a neuroblastoma cell line, we used whole cell patch-clamp methods and reverse transcription-polymerase chain reaction (RT-PCR) to study Na+ currents and channels in B104 cells. We distinguished Tetrodotoxin (TTX)-sensitive and -resistant Na+ currents and detected the mRNA for the cardiac rH1 channel in B104 cells. Na+ currents could be recorded in 65% of cells. In the absence of TTX, mean peak Na+ current density was 126 +/- 19 pA/pF, corresponding to a channel density of 2.7 +/- 0.4/micron 2 (mean +/- SE). Time-to-peak (t-peak), activation (tau m), and inactivation time constants (tau h) for Na+ currents in B104 cells were 1.0 +/- 0.04, 0.4 +/- 0.06, and 0.9 +/- 0.04 ms at -10 mV. The peak conductance-voltage relationship had a V 1/2 of -39.8 +/- 1.5 mV. V 1/2 for steady-state inactivation was -81.6 +/- 1.5 mV. TTX-sensitive and -resistant components of the Na current had half-maximal inhibitions (IC50), respectively, of 1.2 nM and, minimally, 575.5 nM. The TTX-sensitive and -resistant Na+ currents were kinetically distinct; time-to-peak, tau m, and tau h for TTX-sensitive currents were shorter than for TTX-resistant currents. Steady-state voltage dependence of the two currents was indistinguishable. The presence of TTX-sensitive and -resistant Na+ currents, which are pharmacologically and kinetically distinct, led us to search for mRNAs known to be associated with TTX-resistant channels, in addition to the alpha subunit mRNAs, which have previously been shown to be expressed in these cells. Using RT-PCR and restriction enzyme mapping, we were unable to detect alpha SNS, but detected mRNA for rH1, which is known to encode a TTX-resistant channel, in B104 cells. B104 neuroblastoma cells thus express TTX-sensitive and -resistant Na+ currents. These appear to be encoded by neuronal-type and cardiac Na+ channel mRNAs including the RH1 transcript. This cell line may be useful for studies on the rH1 channel, which is known to be mutated in the long-QT syndrome.
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PMID:TTX-sensitive and -resistant Na+ currents, and mRNA for the TTX-resistant rH1 channel, are expressed in B104 neuroblastoma cells. 912 May 65

Nearly 30% of patients treated with metformin experience gastrointestinal side effects. Since release of 5-hydroxytryptamine (5-HT) from the intestine is associated with nausea, vomiting, and diarrhea, we examined whether metformin induces 5-HT release from the intestinal mucosa. In 40% of tissue biopsy specimens of human duodenal mucosa, metformin (1, 10, and 30 microM) caused an increase in 5-HT outflow by 35, 70, and 98%, respectively. Peak increases in 5-HT outflow were observed after 10-15 min exposure to metformin, returning to baseline levels after 25 min. Tetrodotoxin (1 microM) reduced by about 50% the metformin-evoked increase in 5-HT outflow (P<0.05). Metformin-evoked release was not affected by scopolamine + hexamethonium, propranolol, the 5-HT3 receptor antagonist dolasetron, naloxone, or the NK1 receptor antagonist L703606. In the presence of tetrodotoxin (1 microM), somatostatin (1 microM) further reduced metformin-induced 5-HT release by 15-20%. In view of the 5-HT releasing effects of selective 5-HT3 receptor agonists to which metformin (N-N-dimethylbiguanide) is structurally related, we investigated whether metformin directly interacts with 5-HT3 receptors. Receptor binding (inhibition of [3H]-GR65630 binding) and agonist effects (stimulation of [14C]-guanidinium influx) at 5-HT3 receptors were studied in murine neuroblastoma N1E-115 cells, which express functional 5-HT3 receptors. Metformin up to 0.3 mM failed to inhibit [3H]-GR65630 binding and to modify displacement of [3H]-GR65630 binding induced by 5-HT. 5-HT (3 microM) stimulated the influx of [14C]-guanidinium in intact N1E-115 cells. Metformin up to 1 mM failed to modify basal influx, 5-HT-induced influx, and 5-HT+ substance P-induced influx of [14C]-guanidinium. Our results indicate that metformin induces 5-HT3 receptor-independent release of 5-HT from human duodenal mucosa via neuronal and non-neuronal mechanisms. Part of the gastrointestinal side effects observed during treatment with metformin could, thus, be produced by the release of 5-HT and other neurotransmitter substances within the duodenal mucosa.
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PMID:Effects of metformin on intestinal 5-hydroxytryptamine (5-HT) release and on 5-HT3 receptors. 1065 Nov 52

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells.
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PMID:Varicella-zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line. 2338 6


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