Inhibitory effects of volatile anesthetics on K+ and Cl- channel currents in porcine tracheal and bronchial smooth muscle.
BACKGROUND
K+ and Ca2+-activated Cl- (ClCa) channel currents have been shown to contribute to the alteration of membrane electrical activity in airway smooth muscle. This study was conducted to investigate the effects of volatile anesthetics, which are potent bronchodilators, on the activities of these channels in porcine tracheal and bronchial smooth muscles.


METHODS
Whole-cell patch clamp recording techniques were used to investigate the effects of superfused isoflurane (0-1.5 minimum alveolar concentration) or sevoflurane (0-1.5 minimum alveolar concentration) on K+ and ClCa channel currents in dispersed smooth muscle cells.


RESULTS
Isoflurane and sevoflurane inhibited whole-cell K+ currents to a greater degree in tracheal versus bronchial smooth muscle cells. More than 60% of the total K+ currents in tracheal smooth muscle appeared to be mediated through delayed rectifier K+ channels compared with less than 40% in bronchial smooth muscle. The inhibitory effects of the anesthetics were greater on the delayed rectifier K+ channels than on the remaining K+ channels. Cl- currents through ClCa channels were significantly inhibited by the anesthetics. The inhibitory potencies of the anesthetics on the ClCa channels were not different in tracheal and bronchial smooth muscle cells.


CONCLUSIONS
Volatile anesthetics isoflurane and sevoflurane significantly inhibited Cl- currents through ClCa channels, and the inhibitory effect is consistent with the relaxant effect of volatile anesthetics in airway smooth muscle. Different distributions and different anesthetic sensitivities of K+ channel subtypes could play a role in the different inhibitory effects of the anesthetics on tracheal and bronchial smooth muscle contractions.
Chen
Xiangdong
X
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Yamakage
Michiaki
M
Namiki
Akiyoshi
A
D015761:4-Aminopyridine / Q000494:pharmacology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D018999:Charybdotoxin / Q000494:pharmacology; D018118:Chloride Channels / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D000077149:Sevoflurane; D013552:Swine; D014132:Trachea / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018118:Chloride Channels; D008738:Methyl Ethers; D015221:Potassium Channels; D018999:Charybdotoxin; D000077149:Sevoflurane; D015761:4-Aminopyridine; D007530:Isoflurane