Relaxing effects of 5-oxo-ETE on human bronchi involve BKCa channel activation

The present study investigated the ability of 5-oxo-EicosaTetraEnoic acid (5-oxo-ETE) for modulating airway smooth muscle (ASM) tone in human bronchi. 5-Oxo-ETE induced a concentration-dependent relaxing effect on human bronchi pre-contracted with methacholine (MCh) and arachidonic acid (AA). This relaxing response was highly sensitive to Iberiotoxin (IbTx), a large conducting Ca2+-activated K+ channel (BKCa) inhibitor. Furthermore, microelectrode measurements revealed that 5-oxo-ETE (0.1-10 μM) hyperpolarizes the membrane potential of human bronchial ASM cells. These hyperpolarizing effects were also inhibited in the presence of 10 nM IbTx. Lastly, 5-oxo-ETE was shown to directly activate reconstituted BKCa channels derived from human airway smooth muscles. In summary, the 5-oxo-ETE eicosanoid activates a specific K+ conductance, involved in membrane hyperpolarization, which in turn reduces Ca2+ entry and facilitates relaxation of smooth muscle cells.