Resting and Activation-Dependent Ion Channels in Human Mast Cells

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Abstract
The mechanism of mediator secretion from mast cells in disease is likely to include modulation of ion channel activity. Several distinct Ca2+, 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 Ca2+-activated K+ current exhibiting weak inward rectification, which polarized the cells to around −40 mV and a smaller outwardly rectifying Ca2+-independent Cl− conductance. Human lung mast cells showed more heterogeneity in their response to anti-IgE, with Ca2+-activated K+ currents and Ca2+-independent Cl− currents developing in ∼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 Ca2+-activated K+ channel. Charybdotoxin did not consistently attenuate histamine or leukotriene C4 release, indicating that the Ca2+-activated K+ current may enhance, but is not essential for, the release of these mediators.