The repolarizing effects of volatile anesthetics on porcine tracheal and bronchial smooth muscle cells.
This study was conducted to determine the effects of volatile anesthetics (potent bronchodilators) on membrane potentials in porcine tracheal and bronchial smooth muscle cells. We used a current-clamp technique to examine the effects of the volatile anesthetics isoflurane (1.5 minimum alveolar anesthetic concentration [MAC]) and sevoflurane (1.5 MAC) on membrane potentials of porcine tracheal and bronchial (third- to fifth-generation) smooth muscle cells depolarized by a muscarinic agonist, carbachol (1 microM). The effects of volatile anesthetics on muscarinic receptor binding affinity were also investigated by using a radiolabeled receptor assay technique. The volatile anesthetics isoflurane and sevoflurane induced significant repolarization of the depolarized cell membranes in the trachea (from -19.8 to -23.6 mV and to -24.8 mV, respectively) and bronchus (from -24.7 to -29.3 mV and -30.4 mV, respectively) without affecting carbachol binding affinity to the muscarinic receptor. The repolarizing effect was abolished by a Ca(2+)-activated Cl(-) channel blocker, niflumic acid. These results indicate that volatile anesthetic-induced repolarization of airway smooth muscle cell membranes might be caused by a change in Ca(2+)-activated Cl(-) channel activity and that the different repolarized effects of the volatile anesthetics could in part contribute to the different effects of volatile anesthetics on tracheal and bronchial smooth muscle contractions.


CONCLUSIONS
By use of a current-clamp technique, the volatile anesthetics isoflurane and sevoflurane repolarized porcine airway smooth muscle cell membranes depolarized by a muscarinic agonist. This effect might be caused mainly by change in Ca(2+)-activated Cl(-) channel activity, not in K(+) channel activity.
Yamakage
Michiaki
M
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. yamakage@sapmed.ac.jp
Chen
Xiangdong
X
Kimura
Akira
A
Iwasaki
Sohshi
S
Namiki
Akiyoshi
A
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009544:Niflumic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D000077149:Sevoflurane; D013552:Swine; D014132:Trachea / Q000187:drug effects / Q000502:physiology*
D018685:Anesthetics, Inhalation; D002121:Calcium Channel Blockers; D018118:Chloride Channels; D008738:Methyl Ethers; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D000077149:Sevoflurane; D009544:Niflumic Acid; D002217:Carbachol; D007530:Isoflurane