TY - JOUR T1 - The role of the K<sub>Ca</sub>3.1 channel in the regulation of airway mucus hypersecretion in asthma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3896 AU - Greer Arthur AU - Erol Gaillard AU - Peter Bradding Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3896.abstract N2 - The Ca2+-activated potassium channel, KCa3.1, is implicated in the process of exocytic release of intracellular granules from secretory cells such as human lung mast cells (HLMCs). MUC5AC is a human mucin that is upregulated in asthmatic human airways, and is hypothesised to be released from secretory human bronchial epithelial cells (HBECs) via exocytosis of intracellular granules. The aim was to investigate whether KCa3.1 plays a role in MUC5AC synthesis and secretion from HBECs. Expression of MUC5AC and KCa3.1 was investigated in primary HBEC cultures using quantitative RT-PCR and western blotting, and in bronchial biopsies using immunohistochemistry. KCa3.1 activity was examined using patch clamp electrophysiology. KCa3.1 mRNA expression was similar in submerged asthmatic and healthy HBECs, and protein expression was evident in western blots. MUC5AC and KCa3.1 immunoreactivity were demonstrated in the bronchial epithelium in severe, moderate and mild asthmatics, and in healthy controls. MUC5AC and KCa3.1 immunostaining co-localised in approximately 50% of cells. Severe asthmatic bronchial epithelium displayed higher levels of KCa3.1 (P = 0.001) and MUC5AC (P = 0.018) immunostaining. Asthmatic HBECs exhibited larger KCa3.1 currents than healthy HBECs (P = 0.023). Co-localisation of MUC5AC with KCa3.1 immunostaining suggests that mucus-secreting airway epithelial cells express KCa3.1. These results demonstrate the potential for KCa3.1 to contribute to pathological mucus secretion in asthma. ER -