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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2008-6-19
pubmed:abstractText
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 microm) was added to the bath during the recordings. Immunofluorescence studies with selective antibodies against the alpha and beta1 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0958-0670
pubmed:author
pubmed:issnType
Print
pubmed:volume
93
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
908-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Interleukin-4 activates large-conductance, calcium-activated potassium (BKCa) channels in human airway smooth muscle cells.
pubmed:affiliation
Department of Medicine, LRB 319, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural