Sodium tanshinone IIA sulfonate stimulated Cl− secretion in mouse trachea

Sodium tanshinone IIA sulfonate (STS) is a derivate of tanshinone IIA, a lipophilic compound in Salvia miltiorrhiza . This study aimed to investigate the effect of STS on ion transport in mouse tracheal epithelium and the mechanisms underlying it. Short-circuit current ( I sc ) was measured to evaluate the effect of STS on transepithelial ion transport. Intracellular Ca 2+ imaging was performed to observe intracellular Ca 2+ concentration ([Ca 2+ ] i ) changes induced by STS in primary cultured mouse tracheal epithelial cells. Results showed that the apical application of STS at mouse trachea elicited an increase of I sc , which was abrogated by atropine, an antagonist of muscarinic acetylcholine receptor (mAChR). By removing ambient Cl − or applying blockers of Ca 2+ -activated Cl − channel (CaCC), the response of STS-induced I sc was suppressed. Moreover, STS elevated the [Ca 2+ ] i in mouse tracheal epithelial cells. As a result, STS stimulated Cl − secretion in mouse tracheal epithelium via CaCC in an mAChR-dependent way. Due to the critical role of Cl − secretion in airway hydration, our findings suggested that STS may be used to ameliorate the airway dehydration symptom in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).