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This Article Full Text Full Text (PDF) All Versions of this Article: 93/7/908    most recent expphysiol.2008.042432v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Martin, G. Articles by Madison, J. M. PubMed PubMed Citation Articles by Martin, G. Articles by Madison, J. M. Related Collections Respiratory

¹ Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, 303 Belmont Street, Worcester, MA 01604, USA ² Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA

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 µM) was added to the bath during the recordings. Immunofluorescence studies with selective antibodies against the 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.

(Received 23 February 2008; accepted after revision 8 April 2008; first published online 10 April 2008)
Corresponding author J. M. Madison: Department of Medicine, LRB 319, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA. Email: mark.madison{at}umassmed.edu