Effects of sevoflurane on the cAMP-induced short-circuit current in mouse tracheal epithelium and recombinant Cl− (CFTR) and K+ (KCNQ1) channels

An optimal level of airway surface liquid is essential for mucociliary clearance in lungs. The cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) and KCNQ1 channels in tracheal epithelium play key roles in luminal and basolateral membranes, respectively. The aim of this study was to examine the effects of sevoflurane on cAMP-induced chloride secretion by the mouse tracheal epithelium and the modulation of recombinant CFTR and KCNQ1 channels. The equivalent short-circuit current (Isc) of the mouse tracheal epithelium was measured using a flow-type Ussing chamber technique. Inhibition of Na+ absorption was achieved through the luminal application of amiloride. cAMP-dependent Cl− secretion was evoked by forskolin and isobutylmethylxanthine (Fsk/IBMX) applied to the basolateral side. The effect of sevoflurane on CFTR and KCNQ1 channels was assessed using a whole-cell patch clamp in human embryonic kidney 293T cells expressing CFTR and KCNQ1 channels. Fsk/IBMX induced a sustained Isc that was suppressed by the application of sevoflurane [decreased by 49 (4.5)% at 190 µM]. The Fsk/IBMX-induced Isc was also blocked by basolateral application of chromanol 293B, a blocker of the KCNQ1 K+ channel. In KCNQ1-expressing cells, sevoflurane 190 µM reduced the outward currents to 59 (4.9)% at 80 mV. The CFTR current was not affected by sevoflurane (∼360 µM). These results suggest that the inhibition of KCNQ1 underlies sevoflurane-induced decrease in airway secretion.