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Resting and activation-dependent ion channels in human mast cells
S M Duffy1, W J Lawley, E C Conley
1Division of Respiratory Medicine, Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|October 10, 2001
Summary
Human mast cells exhibit Ca(2+)-activated K(+) and Ca(2+)-independent Cl(-) currents upon IgE activation. These ion channels may enhance mediator release but are not essential for histamine or leukotriene C(4) secretion.
Area of Science:
- Immunology
- Cell Physiology
- Ion Channel Biology
Background:
- Mast cells are key players in allergic diseases, releasing mediators like histamine.
- Ion channel activity is implicated in mast cell mediator secretion.
- Previous studies identified ion channels in rodent mast cells, but not in human cells.
Purpose of the Study:
- To characterize ion currents in human mast cells.
- To investigate ion channel activity during IgE-dependent activation in human mast cells.
Main Methods:
- Whole-cell patch clamp technique was used on human lung and peripheral blood mast cells.
- Cells were studied at rest and after IgE-dependent activation.
- Charybdotoxin was used to block K(+) currents.
Main Results:
- Human mast cells were mostly electrically silent at rest.
- IgE activation induced Ca(2+)-activated K(+) currents and Ca(2+)-independent Cl(-) currents in most peripheral blood mast cells.
- Human lung mast cells showed heterogeneous responses, with ~50% exhibiting these currents.
- The K(+) current, blocked by charybdotoxin, resembles intermediate conductance Ca(2+)-activated K(+) channels.
- Charybdotoxin did not abolish mediator release, suggesting a modulatory role for the K(+) current.
Conclusions:
- Human mast cells possess distinct ion channel conductances activated by IgE.
- Ca(2+)-activated K(+) currents may play a role in enhancing, but are not critical for, mediator release from human mast cells.