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.
Duffy
S M
SM
Division of Respiratory Medicine, Institute for Lung Health, University of Leicester Medical School, Leicester, United Kingdom.
Leyland
M L
ML
Conley
E C
EC
Bradding
P
P
D002118:Calcium / Q000494:pharmacology*; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007946:Leukemia, Mast-Cell; D008407:Mast Cells / Q000737:chemistry / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000166:cytology; D014407:Tumor Cells, Cultured
D018118:Chloride Channels; D007473:Ion Channels; D015221:Potassium Channels; D002118:Calcium