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 (I-Ca) in porcine tracheal smooth muscle cells, using the whole cell patch-clamp technique. All three volatile anesthetics significantly inhibited I-Ca in a dose-dependent manner with no apparent shift in the voltage dependence of induced I-Ca. The order of inhibitory potencies for I-Ca 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 I-Ca by the three anesthetics were indistinguishable. We conclude that volatile anesthetics have an inhibitory effect on I-Ca of porcine tracheal smooth muscle cells at clinically relevant concentrations and that the inhibitory potencies of volatile anesthetics on I-Ca are closely related to their lipid-phase solubilities.