Premium
Mast cell activation involves plasma membrane potential‐ and thapsigargin‐sensitive intracellular calcium pools
Author(s) -
Kassel O.,
Amrani Y.,
Landry Y.,
Bronner C.
Publication year - 1995
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1995.tb00530.x
Subject(s) - thapsigargin , intracellular , calcium , calcium in biology , mast cell , chemistry , microbiology and biotechnology , biophysics , membrane , biology , biochemistry , immunology , organic chemistry
Summary— The regulation and role of the intracellular Ca 2+ pools were studied in rat peritoneal mast cells. Cytosolic free calcium concentration ([Ca 2+ ]i) was monitored in fura‐2 loaded mast cells. In the presence of Ca 2+ and K+, compound 48/80 induced a biphasic increase in [Ca 2+ ]i composed of a fast transient phase and an apparent sustained phase. The sustained phase was partially inhibited by the addition of Mn 2+ . DTPA, a cell‐impermeant chelator of Mn 2+ , reversed this inhibition, suggesting that a quenching of fura‐2 fluorescence occurs in the extracellular medium. In the absence of extracellular Ca 2+ , the transient phase, but not the sustained one, could be preserved, provided that mast cells were depolarized. The transient phase was completely abolished by thapsigargin, a microsomal Ca 2+ ‐ATPase inhibitor. Maximum histamine release induced by either compound 48/80 or antigen was obtained in the absence of added Ca 2+ only when mast cells were depolarized. These histamine releases were inhibited by low doses (< 30 nM) of thapsigargin. Thapsigargin at higher doses induced histamine release which was unaffected by changing the plasma membrane potential, but was completely dependent on extracellular Ca 2+ , showing that a Ca 2+ influx is required for thapsigargin‐induced exocytosis. Together, these results suggest that the mobilization of Ca 2+ from thapsigargin sensitive‐intracellular pools induced by compound 48/80 or antigen is sufficient to trigger histamine release. The modulation of these pools by the plasma membrane potential suggest their localization is close to the plasma membrane.