Resting and Activation-Dependent Ion Channels in Human Mast Cells

• Published in: The Journal of immunology (1950) Vol. 167; no. 8; pp. 4261 - 4270
• Main Authors: Duffy, S. Mark, Lawley, Wendy J, Conley, Edward C, Bradding, Peter
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15-10-2001
• Subjects: Adult; Blood Cells - immunology; Cell Degranulation; Electric Conductivity; Fetal Blood; Histamine Release; Humans; Immunoglobulin E; Ion Channel Gating; Ion Channels - physiology; Leukotriene C4 - metabolism; Lung - cytology; Lung - immunology; Mast Cells - immunology; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.8.4261

The mechanism of mediator secretion from mast cells in disease is likely to include modulation of ion channel activity. Several distinct Ca(2+), K(+), and Cl(-) conductances have been identified in rodent mast cells, but there are no data on human mast cells. We have used the whole-cell variant of the patch clamp technique to characterize for the first time macroscopic ion currents in purified human lung mast cells and human peripheral blood-derived mast cells at rest and following IgE-dependent activation. The majority of both mast cell types were electrically silent at rest with a resting membrane potential of around 0 mV. Following IgE-dependent activation, >90% of human peripheral blood-derived mast cells responded within 2 min with the development of a Ca(2+)-activated K(+) current exhibiting weak inward rectification, which polarized the cells to around -40 mV and a smaller outwardly rectifying Ca(2+)-independent Cl(-) conductance. Human lung mast cells showed more heterogeneity in their response to anti-IgE, with Ca(2+)-activated K(+) currents and Ca(2+)-independent Cl(-) currents developing in approximately 50% of cells. In both cell types, the K(+) current was blocked reversibly by charybdotoxin, which along with its electrophysiological properties suggests it is carried by a channel similar to the intermediate conductance Ca(2+)-activated K(+) channel. Charybdotoxin did not consistently attenuate histamine or leukotriene C(4) release, indicating that the Ca(2+)-activated K(+) current may enhance, but is not essential for, the release of these mediators.