抄録
An optimal airway surface liquid is crucial for the mucociliary clearance of lung. In this study, we investigated the effects of sevoflurane on the electrogenic chloride secretion of mouse tracheal epithelium and relevant ion channels. The equivalent short circuit current (Isc′) of mouse tracheal epithelium was measured in a flow-type Ussing chamber study. After inhibiting the background Na+ absorption by luminal application of amiloride, the cAMP-dependent Cl– secretion was evoked by basolateral application of forskolin and isobutylmethylxanthine (Fsk/IBMX). The Fsk/IBMX induced sustained Isc′, which was suppressed by basolateral addition of chromanol 293B, a blocker of KCNQ1 K+ channel. Also, the application of sevoflurane suppressed the Fsk/IBMX-induced Isc′ in a dose-dependent manner. To elucidate the relevant ion channels targeted by sevoflurane, a whole-cell patch clamp was performed with COS7 and HEK293 cells expressing CFTR and KCNQ1 channels, respectively. In KCNQ1-expressing cells, the outward current at 80 mV was reduced to 59 ± 4.9% by 3% sevoflurane. However, the CFTR current was not affected by sevoflurane up to 5% of partial pressure. From this study, it is concluded that the inhibition of KCNQ1 underlies the sevoflurane-induced decrease of airway secretion. [J Physiol Sci. 2007;57 Suppl:S246]