{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:54:14Z","timestamp":1790416454933,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T00:00:00Z","timestamp":1343952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec><jats:title>BACKGROUND AND PURPOSE<\/jats:title><jats:p>Small (K<jats:sub>Ca<\/jats:sub>2) and intermediate (K<jats:sub>Ca<\/jats:sub>3.1) conductance calcium\u2010activated potassium channels (K<jats:sub>Ca<\/jats:sub>) may contribute to both epithelium\u2010 and endothelium\u2010dependent relaxations, but this has not been established in human pulmonary arteries and bronchioles. Therefore, we investigated the expression of K<jats:sub>Ca<\/jats:sub>2.3 and K<jats:sub>Ca<\/jats:sub>3.1 channels, and hypothesized that activation of these channels would produce relaxation of human bronchioles and pulmonary arteries.<\/jats:p><\/jats:sec><jats:sec><jats:title>EXPERIMENTAL APPROACH<\/jats:title><jats:p>Channel expression and functional studies were conducted in human isolated small pulmonary arteries and bronchioles. K<jats:sub>Ca<\/jats:sub>2 and K<jats:sub>Ca<\/jats:sub>3.1 currents were examined in human small airways epithelial (HSAEpi) cells by whole\u2010cell patch clamp techniques.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>While K<jats:sub>Ca<\/jats:sub>2.3 expression was similar, K<jats:sub>Ca<\/jats:sub>3.1 protein was more highly expressed in pulmonary arteries than bronchioles. Immunoreactive K<jats:sub>Ca<\/jats:sub>2.3 and K<jats:sub>Ca<\/jats:sub>3.1 proteins were found in both endothelium and epithelium. K<jats:sub>Ca<\/jats:sub> currents were present in HSAEpi cells and sensitive to the K<jats:sub>Ca<\/jats:sub>2.3 blocker UCL1684 and the K<jats:sub>Ca<\/jats:sub>3.1 blocker TRAM\u201034. In pulmonary arteries contracted by U46619 and in bronchioles contracted by histamine, the K<jats:sub>Ca<\/jats:sub>2.3\/ K<jats:sub>Ca<\/jats:sub>3.1 activator, NS309, induced concentration\u2010dependent relaxations. NS309 was equally potent in relaxing pulmonary arteries, but less potent in bronchioles, than salbutamol. NS309 relaxations were blocked by the K<jats:sub>Ca<\/jats:sub>2 channel blocker apamin, while the K<jats:sub>Ca<\/jats:sub>3.1 channel blocker, charybdotoxin failed to reduce relaxation to NS309 (0.01\u20131\u2003\u00b5M).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS AND IMPLICATIONS<\/jats:title><jats:p>K<jats:sub>Ca<\/jats:sub>2.3 and K<jats:sub>Ca<\/jats:sub>3.1 channels are expressed in the endothelium of human pulmonary arteries and epithelium of bronchioles. K<jats:sub>Ca<\/jats:sub>2.3 channels contributed to endo\u2010 and epithelium\u2010dependent relaxations suggesting that these channels are potential targets for treatment of pulmonary hypertension and chronic obstructive pulmonary disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2012.01986.x","type":"journal-article","created":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T05:40:28Z","timestamp":1334641228000},"page":"37-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Activation of endothelial and epithelial K<sub>Ca<\/sub>2.3 calcium\u2010activated potassium channels by NS309 relaxes human small pulmonary arteries and 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