Effects of sevoflurane 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 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.


METHODS
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.


RESULTS
Fsk/IBMX induced a sustained Isc that was suppressed by the application of sevoflurane [decreased by 49 (4.5)% at 190 microM]. 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 microM reduced the outward currents to 59 (4.9)% at 80 mV. The CFTR current was not affected by sevoflurane (approximately 360 microM).


CONCLUSIONS
These results suggest that the inhibition of KCNQ1 underlies sevoflurane-induced decrease in airway secretion.
Kim
J K
JK
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sung Kyun Kwan University School of Medicine, Seoul 135-710, Republic of Korea.
Yoo
H Y
HY
Kim
S J
SJ
Hwang
Y-S
YS
Han
J
J
Kim
J A
JA
Kim
C S
CS
Cho
H S
HS
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000378:metabolism; D015194:Diffusion Chambers, Culture; D005260:Female; D051657:KCNQ1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D000077149:Sevoflurane; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D018685:Anesthetics, Inhalation; D002712:Chlorides; D051657:KCNQ1 Potassium Channel; C496910:Kcnq1 protein, mouse; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000077149:Sevoflurane; D000242:Cyclic AMP