Voltage‐dependent and calcium‐activated ion channels in the human mast cell line HMC‐1

The mechanisms underlying the recruitment, differentiation, and sustained activation of mast cells in disease are likely to include modulation of ion channels. Specific Ca 2+ , K + , and Cl − conductances have been identified in rodent mast cells, but there are no equivalent data on human mast cells. We have used the whole‐cell patch‐clamp technique to characterize macroscopic ion currents in both the human mast cell line HMC‐1 and human skin mast cells (HSMCs) at rest and in HMC‐1 after activation with calcium ionophore. HSMCs were electrically silent at rest. In contrast, HMC‐1 expressed a strong outwardly rectifying voltage‐dependent Cl − conductance characteristic of ClC‐4 or ClC‐5 and a small inwardly rectifying K + current not carried by the classical Kir family of K + channels. Calcium ionophore induced the appearance of outwardly rectifying Ca 2+ ‐activated Cl − and K + currents, while hypotonicity induced another outwardly rectifying conductance typical of ClC‐3. Reverse transcription‐PCRs confirmed that mRNAs for the voltage‐dependent Cl − channels ClC‐3 and –5 were expressed. This is the first definitive description of a ClC‐4/5‐like current in a native leukocyte. We suggest that this current may contribute to the malignant phenotype while the Ca 2+ ‐activated K + and Cl − currents may be involved in cell activation.