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).