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Interleukin‐4 activates large‐conductance, calcium‐activated potassium (BK Ca ) channels in human airway smooth muscle cells
Author(s) -
Martin Gilles,
O'Connell Robert J.,
Pietrzykowski Andrzej Z.,
Treistman Steven N.,
Ethier Michael F.,
Madison J. Mark
Publication year - 2008
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2008.042432
Subject(s) - bk channel , calcium activated potassium channel , histamine , chemistry , potassium channel , calcium , biophysics , membrane potential , endocrinology , medicine , biology , biochemistry , organic chemistry
Large‐conductance, calcium‐activated potassium (BK Ca ) channels are regulated by voltage and near‐membrane calcium concentrations and are determinants of membrane potential and excitability in airway smooth muscle cells. Since the T helper−2 (Th2) cytokine, interleukin (IL)‐4, is an important mediator of airway inflammation, we investigated whether IL‐4 rapidly regulated BK Ca activity in normal airway smooth muscle cells. On‐cell voltage clamp recordings were made on subconfluent, cultured human bronchial smooth muscle cells (HBSMC). Interleukin‐4 (50 ng ml −1 ), IL‐13 (50 ng ml −1 ) or histamine (10 μ m ) was added to the bath during the recordings. Immunofluorescence studies with selective antibodies against the α and β1 subunits of BK Ca were also performed. Both approaches demonstrated that HBSMC membranes contained large‐conductance channels (>200 pS) with both calcium and voltage sensitivity, all of which is characteristic of the BK Ca channel. Histamine caused a rapid increase in channel activity, as expected. A new finding was that perfusion with IL‐4 stimulated rapid, large increases in BK Ca channel activity (77.2 ± 63.3‐fold increase, P < 0.05, n = 18). This large potentiation depended on the presence of external calcium. In contrast, IL‐13 (50 ng ml −1 ) had little effect on BK Ca channel activity, but inhibited the effect of IL‐4. Thus, HBSMC contain functional BK Ca channels whose activity is rapidly potentiated by the cytokine, IL‐4, but not by IL‐13. These findings are consistent with a model in which IL‐4 rapidly increases near‐membrane calcium concentrations to regulate BK Ca activity.