Volatile anesthetics inhibit voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells.
The relaxation of airway smooth muscle by volatile anesthetics is associated with a decreased concentration of intracellular free Ca2+. We hypothesized that inhibition of the entry of extracellular Ca2+ contributes to the relaxation. We therefore examined the effects of halothane, isoflurane, and sevoflurane on macroscopic voltage-activated Ca2+ currents (ICa) in porcine tracheal smooth muscle cells, using the whole cell patch-clamp technique. All three volatile anesthetics significantly inhibited ICa in a dose-dependent manner with no apparent shift in the voltage dependence of induced ICa. The order of inhibitory potencies for ICa was halothane > isoflurane > sevoflurane. When data were plotted as a function of the estimated anesthetic concentrations in the lipid phase, the potencies for inhibition of ICa by the three anesthetics were indistinguishable. We conclude that volatile anesthetics have an inhibitory effect on ICa of porcine tracheal smooth muscle cells at clinically relevant concentrations and that the inhibitory potencies of volatile anesthetics on ICa are closely related to their lipid-phase solubilities.
Yamakage
M
M
Department of Anesthesiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Hirshman
C A
CA
Croxton
T L
TL
D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D004987:Ethers / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D000077149:Sevoflurane; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
D000777:Anesthetics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D007530:Isoflurane; D006221:Halothane