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

Background. An optimal level of airway surface liquid is essential for mucociliary clearance in lungs. The cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) and KCNQ I 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 KCNQ I channels. Methods. The equivalent short-circuit current (I-sc) 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 CI- secretion was evoked by forskolin and isobutylmethylxanthine (Fsk/IBMX) applied to the basolateral side. The effect of sevoflurane on CFTR and KCNQ I channels was assessed using a whole-cell patch clamp in human embryonic kidney 293T cells expressing CFTR and KCNQ I channels. Results. Fsk/IBMX induced a sustained I-sc that was suppressed by the application of sevoflurane [decreased by 49 (4.5)% at 190 mu M]. The Fsk/IBMX-induced I-sc was also blocked by basolateral application of chromanol 29313, a blocker of the KCNQ I K+ channel. In KCNQ I-expressing cells, sevoflurane 190 mu M reduced the outward currents to 59 (4.9)% at 80 mV The CFTR current was not affected by sevoflurane (similar to 360 mu M). Conclusions. These results suggest that the inhibition of KCNQ I underlies sevoflurane-induced decrease in airway secretion.