The role of the K Ca 3.1 channel in the regulation of airway mucus hypersecretion in asthma

The Ca 2+ -activated potassium channel, K Ca 3.1, 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 K Ca 3.1 plays a role in MUC5AC synthesis and secretion from HBECs. Expression of MUC5AC and K Ca 3.1 was investigated in primary HBEC cultures using quantitative RT-PCR and western blotting, and in bronchial biopsies using immunohistochemistry. K Ca 3.1 activity was examined using patch clamp electrophysiology. K Ca 3.1 mRNA expression was similar in submerged asthmatic and healthy HBECs, and protein expression was evident in western blots. MUC5AC and K Ca 3.1 immunoreactivity were demonstrated in the bronchial epithelium in severe, moderate and mild asthmatics, and in healthy controls. MUC5AC and K Ca 3.1 immunostaining co-localised in approximately 50% of cells. Severe asthmatic bronchial epithelium displayed higher levels of K Ca 3.1 (P = 0.001) and MUC5AC (P = 0.018) immunostaining. Asthmatic HBECs exhibited larger K Ca 3.1 currents than healthy HBECs (P = 0.023). Co-localisation of MUC5AC with K Ca 3.1 immunostaining suggests that mucus-secreting airway epithelial cells express K Ca 3.1. These results demonstrate the potential for K Ca 3.1 to contribute to pathological mucus secretion in asthma.