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 Ca2+, 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 Ca2+-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 Ca2+-activated K+ and Cl- currents may he involved in cell activation.