All-or-none activation of CRAC channels by agonist elicits graded responses in populations of mast cells

Wei Chiao Chang, Joseph Di Capite, Charmaine Nelson, Anant B. Parekh

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

In nonexcitable cells, receptor stimulation evokes Ca2+ release from the endoplasmic reticulum stores followed by Ca2+ influx through store-operated Ca2+ channels in the plasma membrane. In mast cells, store-operated entry is mediated via Ca2+ release-activated Ca 2+ (CRAC) channels. In this study, we find that stimulation of muscarinic receptors in cultured mast cells results in Ca2+-dependent activation of protein kinase Cα and the mitogen activated protein kinases ERK1/2 and this is required for the subsequent stimulation of the enzymes Ca2+-dependent phospholipase A2 and 5-lipoxygenase, generating the intracellular messenger arachidonic acid and the proinflammatory intercellular messenger leukotriene C4. In cell population studies, ERK activation, arachidonic acid release, and leukotriene C4 secretion were all graded with stimulus intensity. However, at a single cell level, Ca2+ influx was related to agonist concentration in an essentially all-or-none manner. This paradox of all-or-none CRAC channel activation in single cells with graded responses in cell populations was resolved by the finding that increasing agonist concentration recruited more mast cells but each cell responded by generating all-or-none Ca2+ influx. These findings were extended to acutely isolated rat peritoneal mast cells where muscarinic or P2Y receptor stimulation evoked all-or-none activation of Ca2+entry but graded responses in cell populations. Our results identify a novel way for grading responses to agonists in immune cells and highlight the importance of CRAC channels as a key pharmacological target to control mast cell activation.

Original languageEnglish
Pages (from-to)5255-5263
Number of pages9
JournalJournal of Immunology
Volume179
Issue number8
Publication statusPublished - Oct 15 2007
Externally publishedYes

Fingerprint

Mast Cells
Population
Leukotriene C4
Arachidonic Acid
Arachidonate 5-Lipoxygenase
Phospholipases A2
Mitogen-Activated Protein Kinase 1
Muscarinic Receptors
Endoplasmic Reticulum
Protein Kinase C
Cholinergic Agents
Cultured Cells
Cell Membrane
Pharmacology
Enzymes

ASJC Scopus subject areas

  • Immunology

Cite this

All-or-none activation of CRAC channels by agonist elicits graded responses in populations of mast cells. / Chang, Wei Chiao; Di Capite, Joseph; Nelson, Charmaine; Parekh, Anant B.

In: Journal of Immunology, Vol. 179, No. 8, 15.10.2007, p. 5255-5263.

Research output: Contribution to journalArticle

Chang, Wei Chiao ; Di Capite, Joseph ; Nelson, Charmaine ; Parekh, Anant B. / All-or-none activation of CRAC channels by agonist elicits graded responses in populations of mast cells. In: Journal of Immunology. 2007 ; Vol. 179, No. 8. pp. 5255-5263.
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