Volatile anesthetics inhibit mucociliary clearance in the airways [1]. The two-pore-domain K⁺-channel, TASK-1, represents one of their molecular targets in that they increase its open probability [2]. Here, we set out to determine whether particle transport speed (PTS) at the mucosal surface of the mouse trachea, a parameter of the cilia-driven mechanism in mucociliary clearance, is regulated by TASK-1.

Tracheas from TASK-1 knockout (KO) mice [3] and corresponding wild-type mice were investigated by immunohistochemistry, Western blot, epithelial laser-assisted microdissection followed by RT-PCR, and by assessment of PTS at the mucosal surface of the explanted and opened trachea.

Laser-assisted microdissection of epithelium/RT-PCR analysis revealed TASK-1 mRNA expression in the tracheal epithelium. Immunodetection of TASK-1 protein in Western blot and immunohistochemistry by available antibodies did not yield reliable results since staining patterns in wild-type and KO mice were indistinguishable. Neither TASK-1 inhibitors (A293, anandamide) nor an activator (isoflurane) had any impact on basal and ATP-stimulated PTS. Avertin, an anesthetic with unclear affinity to TASK-1, reduced basal PTS. In tracheas from TASK-1 KO mice, neither basal nor ATP-stimulated PTS was affected and the avertin effect remained unchanged.

In conclusion, contrary to expectation, TASK-1 plays no role in the regulation of tracheal PTS in mice, and avertin reduces PTS independent from TASK-1.

Literature: [1] Matsuura et al. Anesthesia Analgesia. 2006, 102, 1703–1708. [2] Bayliss et al.Mol Interv.2003, 3, 205–219. [3] Aller et al.Neurosci. 2005, 25, 11455–11467.