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.