SKCa and IKCa channels are involved in epithelium‐dependent relaxation of rat bronchioles

Abstract

We investigated whether Ca2+‐activated K+ channels of small (SKCa) and intermediate (IKCa) conductance are present, and in bronchioles can be modulated by an opener, NS309 (6,7‐dichloro‐1H‐indole‐2,3‐dione 3‐oxime). Immunohistochemical studies were conducted, and segments of rat bronchioles (847 ± 25 μm, n=51) were mounted in microvascular myographs for isometric tension recordings. The effect of NS309 was compared to that in pulmonary arteries. Immunoreaction for IKCa and SKCa3 was found in rat bronchiole epithelium. In 5‐HT (1 µM)‐contracted rat bronchioles, NS309 (0.01‐10 µM) and a β2‐adrenoceptor agonist, salbutamol, induced concentration‐ and epithelium‐dependent relaxations. An inhibitor of cyclooxygenase, indomethacin (3 µM), a NO‐synthase inhibitor, L‐NNA (100 µM) and a CYP2C9 inhibitor, sulphaphenazole (100 µM), did not reduce NS309 relaxation. In contrast to a blocker of large‐conductance KCa (BKCa) channels, iberiotoxin (0.1 µM), a blocker of IKCa and BKCa channels, charybdotoxin (0.07 µM) and a blocker of SKCa channels, apamin (0.5 μM), reduced salbutamol and NS309‐induced relaxation. The study suggests that IKCa and SKCa3 channels are located in rat bronchiole epithelium, and that activation of SKCa and IKCa channels by NS309 leads to epithelium‐derived hyperpolarizing factor (EpDHF)‐type relaxation of bronchioles analogue to the EDHF‐type relaxation in rat pulmonary arteries.