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

1. Action potentials elicited in solutions with elevated [Ca2+] (1.8-40 mM) have been studied in differentiated cells of mouse neuroblastoma clone N1E-115 in tissue culture. 2. The action potential in high [Ca2+] solutions containing eithr Na+ or Tris is followed by a prolonged after-hyperpolarization (a.h.p.) lasting 0.5-4 sec. The a.h.p. reverses sign between -75 and -85 mV. 3. Externally applied tetraethylammonium (TEA, 15 mM) increases the Ca2+ spike overshoot, prolongs the falling phase and enhances the a.h.p. duration. The a.h.p. is inhibited by Ca2+ antagonists such as La3+, Co2+ and Mn2+. 4. After replacement of Ca2+ by Ba+ or Sr2+ (20mM) action potentials can still be elicited in Na+-free solution, but no a.h.p. is observed. 5. Increasing [Ca2+] from 1.8 up to 20 mM results in an increased capability of neuroblastoma cells to fire repetitively and in a consistent reduction of the firing rate from about 4-10 sec-1 to 0.5-1.8 sec-1. 6. It is concluded that Ca2+ entry during the action potential activates a TEA-resistant K+ conductance which gives rise to the prolonged a.h.p. Data from repetitively firing cells are consistent with the view that the a.h.p. plays a role in the regulation of low-frequency firing.
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PMID:The calcium action potential and a prolonged calcium dependent after-hyperpolarization in mouse neuroblastoma cells. 49 Mar 57

1. The Ca2+ inward current (ICa) and a slow outward current in differentiated cells of mouse neuroblastoma clone N1E-115 have been studied under voltage-clamp conditions. 2. ICa shows voltage- and time-dependent inactivation when evoked by step-wise depolarizations in Na+-free solution containing high [Ca2+] (20 nM) and tetraethylammonium (TEA, 25 mM). Ba2+ and Sr2+ can substitute for Ca2+. 3. Holding potentials below -70 mV maximal activate ICa. Half inactivation occurs at -56 mV and ICa is completely inactivated beyond holding levels of -30 mV. Maximum peak currents are of the order of 10(-4) A/cm2 and the reversal potential ranges from +40 to +60 mV. The ICa inactivation time course follows first-order kinetics with a voltage-depedent time constant ranging from 25 to 100 msec. 4. The striking resemblance between ICa and the Ca2+ current in the unfertilized mouse oocyte (Okamoto, Takahashi & Yamashita, 1977) is discussed. 5. A slow outward current with a rise time of several seconds is recorded on voltage steps beyond -20 mV in high [Ca2+] solutions. It is carried primarily by K+ on account of the value of the reversal potential and its dependence on [K]0. This K+ current is TEA-insensitive and is blocked by Ca2+ antagonists. 6. The slow K+ current (IK(Ca)) is suggested to be mediated by Ca2+ influx, but the voltage-dependence of the underlying conductance (GK(Ca)) differs significantly from the ICa voltage-dependence. 7. The results are consistent with the hypothesis that IK(Ca) depends both on ICa and on membrane potential. An alternative hypothesis is briefly discussed.
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PMID:The calcium current and the activation of a slow potassium conductance in voltage-clamped mouse neuroblastoma cells. 49 Mar 59

1. Ionic currents in differentiated cells of mouse neuroblastoma clone N1E-115 have been studied under voltage-clamp conditions. 2. Depolarizing voltage steps from a holding potential of -85 mV to levels more positive than -40 mV produced fast transient inward currents followed by delayed outward currents. 3. The fast inward current is carried by Na+: it is blocked by tetrodotoxin and is absent in Na+-free solutions. Its kinetic behaviour resembles that of the Na+ current in squid giant axon. A mean value of 85 mmho/cm2 was found for the maximum Na+ conductance (GNa).4. The delayed outward current is carried primarily by K+: it is blocked by externally applied tetraethylammonium (TEA, 15 mM) and has a reversal potential (mean -71 mV) close to the theoretical K+ equilibrium potential. Its instantaneous I--V curve is linear. By analogy with the formulation of Hodgkin & Huxley (1952c), the outward current can be described by IK = -GKn2(V--EK) where GK = 12 mmho/mc2. 5. During prolonged depolarizations the delayed outward current declines. This decline, which occurs in two phases, represents a partial inactivation of the K+ conductance. 6. A weak inward current with slow activation and inactivation kinetics appears in Na+-free solution containing 10 mM-Ca2+. It is activated at a membrane potential of -55 mV and reaches its maximum at -20 mV with a time to peak of about 10 msec. This current is tetrodotoxin-resistant, reversibly blocked by Co2+ (5mM) and is suggested to be carried by Ca2+. 7. An increase in the external divalent cation concentration results in a parallel shift of the steady-state I--V curve along the voltage axis in positive direction. The activation of delayed outward currents is suggested not to depend on Ca2+ influx. 8. It is concluded that separate voltage-dependent Na+, K+ and Ca2+ channels exist in the differentiated neuroblastoma membrane with kinetic and pharmacological properties similar to those observed in non-mammalian preparations.
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PMID:Ionic currents in cultured mouse neuroblastoma cells under voltage-clamp conditions. 67 Dec 97

GEA 857 [2-(4-chlorophenyl)-1,1-dimethylethyl 2-amino-3-methylbutanoate], a structural analogue of the serotonin (5-HT) uptake inhibitor alaprocalate but without effects on the 5-HT uptake, was shown to potentiate muscarinic cholinergic responses in N1E-115 neuroblastoma cells. In intracellular recording experiments, GEA 857 (1 microM) increased the cell input resistance and prolonged the action potential. It also prolonged the cellular response to carbachol acting on muscarinic receptors in a manner mimicked by potassium channel blockers such as 4-aminopyridine and TEA. GEA 857 did not affect the carbachol stimulated uptake of 45Ca, but depressed the carbachol activated outflow of 86Rb from neuroblastoma cells. The conclusion drawn from these results is that GEA 857 reduces potassium conductances in the membrane in N1E-115 neuroblastoma cells and, thereby, prolongs muscarinic agonist-induced responses.
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PMID:GEA 857 blocks potassium channels in the membrane and, thereby, prolongs muscarinic cholinergic responses in N1E-115 neuroblastoma cells. 130 Oct 72

When exposed to hypotonic solutions, clonal N1E115 neuroblastoma cells initially swell and later undergo a regulatory volume decrease (RVD). We studied the effects of a variety of transport inhibitors on the time course of cross-sectional area of N1E115 cells exposed to a solution of reduced osmolarity (pi = 186 mosm). Application to the bath of either: (i) blockers of net K efflux through K channels (e.g. isotonic KCl or 20 mM TEA); or (ii) blockers of net efflux through anion channels (e.g. isotonic methanesulfonate, 10 microM DIDS or 100 microM IAA-94) all prevent RVD. In contrast, ouabain (a Na+/K+ pump blocker), bumetanide (a Na+/K+/Cl- cotransporter blocker) and SITS (a HCO3-/Cl- exchange blocker) do not. These data support the involvement of these channels over pumps or exchangers in solute exit during RVD. Only variable block of RVD was achieved using blockers of stretch activated non-selective cation C+ (SA) channels (i.e., amiloride and gadolinium, Gd3+) or a membrane permeant Ca chelator (BAPTA-AM) suggesting that neither the opening of C+ (SA) channels nor a global rise in cytosolic Ca2+ is critical for triggering RVD.
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PMID:Pharmacology of volume regulation following hypotonicity-induced cell swelling in clonal N1E115 neuroblastoma cells. 758 68

The biological effects of ceruloplasmin have been exclusively ascribed to its roles as a copper carrier and an antioxidant. Although neuronal involvement of ceruloplasmin is closely related to aging and certain neuronal disorders, neuronal effects of ceruloplasmin are unknown and the possible modulation of membrane potential and ion channels by ceruloplasmin has not been investigated. In the present study, the membrane electrical properties of neuroblastoma cells in the presence of ceruloplasmin were studied using the patch-clamp technique. Ceruloplasmin induced a rapid and sustained membrane depolarization. This capacity of ceruloplasmin was abolished either when the copper was removed from ceruloplasmin or when ceruloplasmin was heat-inactivated. The depolarizing effect of ceruloplasmin was not due to an enhanced Ca2+ or Na+ influx but it seemed to result from a reduced K+ efflux since ceruloplasmin significantly inhibited a TEA-sensitive delayed rectifier K+ channel. To our knowledge, this is the first report which indicates that ceruloplasmin is an endogenous neuronal depolarizing factor.
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PMID:Ceruloplasmin: an endogenous depolarizing factor in neurons? 786 49

1. A variety of studies have suggested that K+ channel activity is a key determinant for cell progression through the G1 phase of mitosis. We have previously proposed that K+ channels control the activity of cell cycle-regulating proteins via regulation of cell volume. In order to test this hypothesis, we measured, with a Coulter counter and under different experimental conditions, the volume and rate of proliferation of neuroblastoma x glioma hybrid NG108-15 cells. 2. The K+ channel blockers TEA (1-10 mM), 4-aminopyridine (0.2-2 mM) and Cs+ (2.5-10 mM) increased the cell volume and decreased the rate of cell proliferation. Proliferation was fully inhibited when cell volume was increased by 25 %. 3. A 40 % increase in the culture medium osmolarity with NaCl induced a 25 % increase in cell volume and an 82 % decrease in the rate of cell proliferation. A 40 % increase in the culture medium osmolarity with mannitol induced a 9 % increase in cell volume and a 60 % decrease in the rate of cell proliferation. 4. The Cl- channel blocker NPPB (5-nitro-2-(3-phenylpropylamino) benzoic acid; 50 microM) induced a 12 % increase in cell volume and a 77 % decrease in the rate of cell proliferation. 5. A 24 % reduction in the culture medium osmolarity with H2O induced a 21 % decrease in cell volume and a 32 % increase in the rate of cell proliferation. 6. Under whole-cell patch-clamp conditions, antibiotics (penicillin plus streptomycin) decreased the voltage-dependent K+ current. Omission of antibiotics from the culture medium induced a 10 % decrease in the cell volume and a 32 % increase in the rate of cell proliferation. 7. These results suggest that the mechanisms controlling cell proliferation are strongly influenced by the factors which determine cell volume. This could take into account the role in mitogenesis of K+ channels and of other ionic pathways involved in cell volume regulation.
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PMID:K+ channel block-induced mammalian neuroblastoma cell swelling: a possible mechanism to influence proliferation. 962 69

The KCNQ family of K(+) channels has been implicated in several cardiac and neurological disease pathologies. KCNQ2 (Q2) is a brain-derived gene, which in association with KCNQ3 (Q3) has been shown to provide a molecular basis for the neuronal M current. We have cloned a long (Q2L) and a short (Q2S) splice variant of the human KCNQ2 gene; these variants differ in their C-terminal tail. Northern blot analysis reveals that Q2L is preferentially expressed in differentiated neurons, whereas the Q2S transcript is prominent in fetal brain, undifferentiated neuroblastoma cells, and brain tumors. Q2L, transfected into mammalian cells, produces a slowly activating, noninactivating voltage-gated K(+) current that is blocked potently by tetraethylammonium (TEA; IC(50), 0.14 mm). Q2S on the other hand produces no measurable potassium currents. Cotransfection of Q2S with either Q2L, Q3, or Q2L/Q3 heteromultimers results in attenuation of K(+) current, the suppression being most profound for Q3. Inclusion of Q2S in the heteromultimer also positively shifts the voltage dependence of current activation and alters affinity for the TEA block, suggesting that under these conditions, some Q2S subunits incorporate into functional channels on the plasma membrane. In view of the crucial role of M currents in modulating neuronal excitability, our findings provide important insight into the functional consequences of differential expression of KCNQ2 splice variants: dampened potassium conductances in the developing brain could shape firing repertoires to provide cues for proliferation rather than differentiation.
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PMID:Differential expression of kcnq2 splice variants: implications to m current function during neuronal development. 1116 Mar 79

Cellular volume loss or shrinkage is a ubiquitous feature of apoptosis and thus may contribute to this form of degeneration. Chloride (Cl(-)) and potassium (K(+)) efflux has been shown to participate in volume regulation and several recent reports have implicated K(+) efflux in apoptotic neuronal death. Here pharmacological inhibitors of various K(+) and Cl(-) channels and transporters were used to decipher the relationship between cellular volume regulation and apoptosis. Following exposure to a hypotonic media, cells swell but over time gradually recover, returning to their original cell volume in a process known as regulatory volume decrease (RVD). RVD in N1E 115 neuroblastoma cells was monitored using time-lapse videomicroscopy, cell size and DNA degradation were followed using flow cytometry and fragmented apoptotic nuclei were visualized using Hoechst staining. RVD was blocked by high K(+), TEA and 4-AP (K(+) channel blockers), DIDS and niflumic acid but not SITS (Cl(-) channel blockers), ethacrynic acid (Cl(-) pump blocker), bumetanide (Na(+)/K(+)/Cl(-) cotransporter blocker) and furosemide (K(+)/Cl(-) cotransport blocker). In contrast, only DIDS and SITS (blockers of the Cl(-)/HCO(3) exchanger) inhibited apoptosis, suggesting that a common mechanistic link between RVD and apoptosis is the Cl(-)/HCO(3) exchanger. Thus, this study does not support the notion that K(+) channels are universal anti-apoptotic targets. Instead, the Cl(-)/HCO(3) exchanger may prove to be a viable target of therapeutic intervention for treating pathological apoptosis and neurodegeneration.
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PMID:Disparity between ionic mediators of volume regulation and apoptosis in N1E 115 mouse neuroblastoma cells. 1210 Oct 47

In N1E 115 neuroblastoma cells, gamma-dendrotoxin (DTX, 200 nM) blocked the outward K(+) current by 31.1 +/- 3.5% (n = 4) with approximately 500 nM Ca(2+) in the pipet solution, but had no effect on the outward K(+) current when internal Ca(2+) was reduced. Using a ramp protocol, iberiotoxin (IbTX, 100 nM) inhibited a component of the whole cell current, but in the presence of 200 nM gamma-DTX, no further inhibition by IbTX was observed. Two types of single channels were seen using outside-out patches when the pipette free Ca(2+) concentration was approximately 500 nM; a 63 pS and a 187 pS channel. The 63 pS channel was TEA-, IbTX- and gamma-DTX-insensitive, while the 187 pS channel was blocked by 1 mM TEA, 100 nM IbTX or 200 nM gamma-DTX. Both channels were activated by external application of ionomycin, when the pipet calcium concentration was reduced. gamma-DTX (200 nM) reduced the probability of openings of the 187 pS channel, with an IC(50) of 8.5 nM. In GH(3) cells gamma-DTX (200 nM) also blocked an IbTX-sensitive component of whole-cell K(+) currents. These results suggest that gamma-DTX blocks a large conductance Ca(2+) activated K(+) current in N1E 115 cells. This is the first indication that any of the dendrotoxins, which have classically been known to block voltage-gated (Kv) channels, can also block Ca(2+) activated K(+) channels.
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PMID:Gamma-dendrotoxin blocks large conductance Ca2+-activated K+ channels in neuroblastoma cells. 1294 32


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