Block of current through T‐type calcium channels by trivalent metal cations and nickel in neural rat and human cells.

Mlinar, Boris; Enyeart, John J.

doi:10.1113/jphysiol.1993.sp019835

Cited by 139 publications

(91 citation statements)

References 28 publications

(30 reference statements)

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“…Reports of blockade of transmembrane calcium flux by lanthanides in skeletal muscle, 26 endothelial cells, 27 pituitary cells, 28 thyroid cells, 29 and neutrophils 47 raised the possibility that GD might impair calcium signaling in the KC as well. Such an effect would be pertinent to our results, because there is evidence of calcium-dependent PGE 2 synthesis in macrophages in general 35,37,38,42 and KC specifically.…”

Section: Figmentioning

confidence: 99%

“…24 This possibility has been supported by the recognition of GD' s potent ability to block calcium channels in muscle cells, 26 endothelial cells, 27 and neuroendocrine cells. 28 The ability of the chelating agents, ethylene glycol-bis(␤-aminoethyl-ether)-N,N-tetraacetic acid, 29 and the orthophosphate salts, NaH 2 PO 4 and KH 2 PO 4 , 30 to reverse the GD blockage suggest that GD ions act extracellularly, probably near the mouth of the Ca ϩϩ channel. The failure of lathanide to affect the 340-nm and 380-nm excitation of fura-2-loaded cells also strongly suggested an extracellular effect.…”

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confidence: 99%

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Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

et al. 1999

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Hepatic Kupffer cells (KC), the major tissue macrophage population, produce the septic response mediators, tumor necrosis factor ␣ (TNF-␣) and prostaglandin E 2 (PGE 2 ), and have been shown to internalize gadolinium chloride (GD), a rare earth metal of the lanthanide series. Because GD pretreatment of rats has been shown to inhibit the mortality of sepsis, we studied the secretory response to lipopolysaccharide (LPS) by KC isolated from rats injected with either saline or GD (7 mg/kg, intravenously) on the 2 days before KC isolation. Using culture conditions modified to reflect the intrasinusoidal milieu of arginine (RPMI-1640 media with 10 or 100 mol/L arginine), KC from GD-treated rats responded to LPS (0.0025 g/mL) with significantly (P F .01) reduced PGE 2 release. In contrast, TNF-␣ release by treated KC was significantly (P F .05) enhanced, consistent with the loss of PGE 2 autocoid inhibition of TNF-␣. Calcium flux is an early signaling event in eicosanoid synthesis, and GD is known to block calcium channels. Therefore, KC were loaded with fura-2-AM to study the effect of GD on KC calcium flux. GD prevented ionomycin and platelet-activating factor (PAF)-mediated [Ca ؉؉ ] i increase and calcium-dependent PGE 2 synthesis, while GD did not affect PGE 2 synthesis when protein kinase C (PKC) was directly activated with tetradecanoylphorbolacetate (TPA). The inhibition of calcium flux and calciumdependent PGE 2 synthesis in the major cell of the monocytic phagocytic system by GD may explain the previously reported ability of this lanthanide to prevent the mortality of endotoxemia. (HEPATOLOGY 1999;29:756-765.)

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Section: Figmentioning

confidence: 99%

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confidence: 99%

Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

et al. 1999

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“…Trivalent ions (e.g., lanthanum, La 3ϩ ) have been used to inhibit connexin hemichannels (7,68,315), but care is required because such ions also block Ca 2ϩ channels (235,407). Similarly, a reduction of the extracellular Ca 2ϩ concentration can trigger connexin hemichannel opening (20,46,131,342,343,405) without influencing gap junctions or pannexin channels.…”

Section: A Inhibitors Of Gap Junction Couplingmentioning

confidence: 99%

Intercellular Ca²⁺Waves: Mechanisms and Function

Leybaert

Sanderson

2012

Physiological Reviews

275

290

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Intercellular calcium (Ca 2ϩ ) waves (ICWs) represent the propagation of increases in intracellular Ca 2ϩ through a syncytium of cells and appear to be a fundamental mechanism for coordinating multicellular responses. ICWs occur in a wide diversity of cells and have been extensively studied in vitro. More recent studies focus on ICWs in vivo. ICWs are triggered by a variety of stimuli and involve the release of Ca 2ϩ from internal stores. The propagation of ICWs predominately involves cell communication with internal messengers moving via gap junctions or extracellular messengers mediating paracrine signaling. ICWs appear to be important in both normal physiology as well as pathophysiological processes in a variety of organs and tissues including brain, liver, retina, cochlea, and vascular tissue. We review here the mechanisms of initiation and propagation of ICWs, the key intra-and extracellular messengers (inositol 1,4,5-trisphosphate and ATP) mediating ICWs, and the proposed physiological functions of ICWs.

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“…The trivalent cations, Y 3ϩ , La 3ϩ , and other lanthanides, have been reported to block differentially the T-type and HVA Ca 2ϩ channels. The smaller cations are more potent T-type antagonists, and the IC 50 for Y 3ϩ blocking of T-type channels is ϳ0.1 nM (Mlinar and Enyeart, 1993). We tested the dose-response of Y 3ϩ on T-type and HVA currents.…”

Section: The Reduction Of T-type Currents By Serotonin Increased R-b mentioning

confidence: 99%

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

Sun

Dale

1997

J. Neurosci.

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The primary sensory Rohon-Beard (R-B) neurons of Xenopus larvae are highly analogous to the C fibers of the mammalian pain pathway. We explored the actions of 5-HT by studying the modulation of Ca 2ϩ currents. In ϳ80% of the acutely isolated R-B neurons, 5-HT inhibited the high voltage-activated (HVA) currents by 16% (n ϭ 29) and the T-type currents by 24% (n ϭ 41). The modulation of the T-type and the HVA currents was mimicked by selective 5-HT 1A and 5-HT 1D agonists: 8-OH-DPAT and L-694,247. The effects of the agonists were blocked by their respective 5-HT 1A or 5-HT 1D antagonists: p-MPPI and GR127935, suggesting that both 5-HT 1A and 5-HT 1D receptors were involved. Approximately 70% of the actions of 5-HT on HVA currents was occluded by -conotoxin-GVIA (N-type channel blocker), whereas the rest of the modulation (ϳ30%) was occluded by Ͻ100 nM -agatoxin-TK (P/Q-type channel blocker). This suggests that 5-HT acts on N-and P/Q-type Ca 2ϩ channels. Neither the modulation of the T-type nor that of the HVA currents was accompanied by changes in their voltage-dependent kinetics. Cell-attached patch-clamp recordings suggest that the modulation of the T-type channel occurs through a membrane-delimited second messenger. We have studied the functional consequences of the modulation of T-type Ca 2ϩ channels and have found that these channels play a role in spike initiation in R-B neurons. Modulation of T-type channels by 5-HT therefore could modulate the sensitivity of this sensory pathway by increasing the thresholds of R-B neurons. This is a new and potentially important locus for modulation of sensory pathways in vertebrates.

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Block of current through T‐type calcium channels by trivalent metal cations and nickel in neural rat and human cells.

Cited by 139 publications

References 28 publications

Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

Intercellular Ca²⁺Waves: Mechanisms and Function

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae

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Block of current through T‐type calcium channels by trivalent metal cations and nickel in neural rat and human cells.

Cited by 139 publications

References 28 publications

Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

Gadolinium blocks rat kupffer cell calcium channels: Relevance to calcium-dependent prostaglandin E2 synthesis and septic mortality

Intercellular Ca2+Waves: Mechanisms and Function

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca2+Currents in the Primary Sensory Neurons ofXenopusLarvae

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Product

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Intercellular Ca²⁺Waves: Mechanisms and Function

Serotonergic Inhibition of the T-Type and High Voltage-Activated Ca²⁺Currents in the Primary Sensory Neurons ofXenopusLarvae