Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin and cetiedil

Narenjkar, Jamshid; Marsh, Stephen J.; Assem, El-Sayed K.

doi:10.1016/j.ejphar.2003.10.013

Cited by 9 publications

(19 citation statements)

References 74 publications

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“…K Ca 3.1 opening is not required for, but potentiates, mast cell secretion (29,30,38) and plays a vital role in cell migration (41). The effect of drugs able to block K Ca 3.1 also suggested that the channel was present in the RBL-2H3 mast cell line (39,40). The present study demonstrates for the first time that mouse BMMCs indeed express K Ca 3.1, and that BMMCs derived from K Ca 3.1-deficient mice completely lack Ca 2ϩ -activated K ϩ channel activity.…”

Section: Discussionmentioning

confidence: 54%

“…However, in the RBL-2H3 rat mast cell line charybdotoxin and the nonselective blocker cetiedil did attenuate degranulation and activation-dependent hyperpolarization of the plasma membrane (38,39). However, another K Ca 3.1 blocker clotrimazole had no effect in these cells at pharmacologically relevant concentrations (39,40). The precise role that K Ca 3.1 plays in mast cell mediator release is therefore unclear, although its presence does appear to be important for human lung mast cell migration (41).…”

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confidence: 99%

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Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca2+-Activated K+ Channel KCa3.1

Shumilina

Lam

Wölbing

et al. 2008

The Journal of Immunology

103

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Mast cell stimulation by Ag is followed by the opening of Ca2+-activated K+ channels, which participate in the orchestration of mast cell degranulation. The present study has been performed to explore the involvement of the Ca2+-activated K+ channel KCa3.1 in mast cell function. To this end mast cells have been isolated and cultured from the bone marrow (bone marrow-derived mast cells (BMMCs)) of KCa3.1 knockout mice (KCa3.1−/−) and their wild-type littermates (KCa3.1+/+). Mast cell number as well as in vitro BMMC growth and CD117, CD34, and FcεRI expression were similar in both genotypes, but regulatory cell volume decrease was impaired in KCa3.1−/− BMMCs. Treatment of the cells with Ag, endothelin-1, or the Ca2+ ionophore ionomycin was followed by stimulation of Ca2+-activated K+ channels and cell membrane hyperpolarization in KCa3.1+/+, but not in KCa3.1−/− BMMCs. Upon Ag stimulation, Ca2+ entry but not Ca2+ release from intracellular stores was markedly impaired in KCa3.1−/− BMMCs. Similarly, Ca2+ entry upon endothelin-1 stimulation was significantly reduced in KCa3.1−/− cells. Ag-induced release of β-hexosaminidase, an indicator of mast cell degranulation, was significantly smaller in KCa3.1−/− BMMCs compared with KCa3.1+/+ BMMCs. Moreover, histamine release upon stimulation of BMMCs with endothelin-1 was reduced in KCa3.1−/− cells. The in vivo Ag-induced decline in body temperature revealed that IgE-dependent anaphylaxis was again significantly (by ∼50%) blunted in KCa3.1−/− mice. In conclusion, KCa3.1 is required for Ca2+-activated K+ channel activity and Ca2+-dependent processes such as endothelin-1- or Ag-induced degranulation of mast cells, and may thus play a critical role in anaphylactic reactions.

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Section: Discussionmentioning

confidence: 54%

mentioning

confidence: 99%

Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca2+-Activated K+ Channel KCa3.1

Shumilina

Lam

Wölbing

et al. 2008

The Journal of Immunology

103

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“…It does not appear that the effects of NaHS-PC to prevent mucosal mitochondrial dysfunction can be attributed to a direct action on neutrophils or mast cells during I/R since recent reports indicate that BK Ca channel activity is absent in both human and mouse neutrophils whereas mast cell function is not inhibited by iberiotoxin, a highly selective BK Ca channel inhibitor (7,31). On the other hand, platelets express BK Ca channels, which, when activated, hyperpolarize platelet membranes, thereby limiting P-selectin expression and platelet adhesion to endothelial cells under static and flow conditions (22).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia-reperfusion-induced mitochondrial dysfunction in rat small intestine

Liu¹,

Kalogeris²,

Wang³

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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The objectives of this study were to determine whether neutrophil depletion with anti-neutrophil serum (ANS) or preconditioning with the hydrogen sulfide (H2S) donor NaHS (NaHS-PC) 24 h prior to ischemia-reperfusion (I/R) would prevent postischemic mitochondrial dysfunction in rat intestinal mucosa and, if so, whether calcium-activated, large conductance potassium (BKCa) channels were involved in this protective effect. I/R was induced by 45-min occlusion of the superior mesenteric artery followed by 60-min reperfusion in rats preconditioned with NaHS (NaHS-PC) or a BKCa channel activator (NS-1619-PC) 24 h earlier or treated with ANS. Mitochondrial function was assessed by measuring mitochondrial membrane potential, mitochondrial dehydrogenase function, and cytochrome c release. Mucosal myeloperoxidase (MPO) and TNF-α levels were also determined, as measures of postischemic inflammation. BKCa expression in intestinal mucosa was detected by immunohistochemistry and Western blotting. I/R induced mitochondrial dysfunction and increased tissue MPO and TNF-α levels. Although mitochondrial dysfunction was attenuated by NaHS-PC or NS-1619-PC, the postischemic increases in mucosal MPO and TNF-α levels were not. The protective effect of NaHS-PC or NS-1619-PC on postischemic mitochondrial function was abolished by coincident treatment with BKCa channel inhibitors. ANS prevented the I/R-induced increase in tissue MPO levels and reversed mitochondrial dysfunction. These data indicate that neutrophils play an essential role in I/R-induced mucosal mitochondrial dysfunction. In addition, NaHS-PC prevents postischemic mitochondrial dysfunction (but not inflammation) by a BKCa channel-dependent mechanism.

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“…Accordingly, cell membrane depolarization decreases Ca 2+ influx and subsequent degranulation [28][29][30]. Ca 2+ -activated K + channels are critical in this scenario, as pharmacological inhibition of these channels disrupts mast cell degranulation [31,32]. Most recently it was shown that the Ca 2+ -activated K + channel in mouse BMMCs is absent in gene targeted mice lacking K Ca 3.1 channels and that K Ca 3.1 is a critical regulator of mast cell degranulation [33].…”

Section: Introductionmentioning

confidence: 99%

Phosphatidylinositol-3-Kinase Regulates Mast Cell Ion Channel Activity

Lam

Shumilina²,

Matzner³

et al. 2008

Cell Physiol Biochem

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Stimulation of the mast cell IgE-receptor (FcεRI) by antigen leads to stimulation of Ca²⁺ entry with subsequent mast cell degranulation and release of inflammatory mediators. Ca²⁺ further activates Ca²⁺-activated K⁺ channels, which in turn provide the electrical driving force for Ca²⁺ entry. Since phosphatidylinositol (PI)-3-kinase has previously been shown to be required for mast cell activation and degranulation, we explored, whether mast cell Ca²⁺ and Ca²⁺-activated K⁺ channels may be sensitive to PI3-kinase activity. Whole-cell patch clamp experiments and Fura-2 fluorescence measurements for determination of cytosolic Ca²⁺ concentration were performed in mouse bone marrow-derived mast cells either treated or untreated with the PI3-kinase inhibitors LY-294002 (10 µM) and wortmannin (100 nM). Antigen-stimulated Ca²⁺ entry but not Ca²⁺ release from the intracellular stores was dramatically reduced upon PI3-kinase inhibition. Ca²⁺ entry was further inhibited by TRPV blocker ruthenium red (10 µM). Ca²⁺ entry following readdition after Ca⁺-store depletion with thapsigargin was again decreased by LY-294002, pointing to inhibition of store-operated channels (SOCs). Moreover, inhibition of PI3-kinase abrogated IgE-stimulated, but not ionomycin-induced stimulation of Ca²⁺-activated K⁺ channels. These observations disclose PI3-kinase-dependent regulation of Ca²⁺ entry and Ca²⁺-activated K⁺-channels, which in turn participate in triggering mast cell degranulation.

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Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin and cetiedil

Cited by 9 publications

References 74 publications

Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca2+-Activated K+ Channel KCa3.1

Blunted IgE-Mediated Activation of Mast Cells in Mice Lacking the Ca2+-Activated K+ Channel KCa3.1

Hydrogen sulfide preconditioning or neutrophil depletion attenuates ischemia-reperfusion-induced mitochondrial dysfunction in rat small intestine

Phosphatidylinositol-3-Kinase Regulates Mast Cell Ion Channel Activity

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