Journal
EXPERIMENTAL PHYSIOLOGY
Volume 93, Issue 7, Pages 908-918Publisher
WILEY
DOI: 10.1113/expphysiol.2008.042432
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Funding
- NHLBI NIH HHS [R01 HL054143, R01 HL054143-10] Funding Source: Medline
- NIAAA NIH HHS [R37 AA012054-11, R01 AA017920, R01 AA018038-02, R01 AA018038, R37 AA012054] Funding Source: Medline
- NIGMS NIH HHS [P20 GM103642] Funding Source: Medline
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Large-conductance, calcium-activated potassium (BKCa) 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 BKCa 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 mu M) was added to the bath during the recordings. Immunofluorescence studies with selective antibodies against the alpha and beta 1 subunits of BKCa 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 BKCa 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 BKCa 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 BKCa channel activity, but inhibited the effect of IL-4. Thus, HBSMC contain functional BKCa 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 BKCa activity.
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