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  • Title: Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells.
    Author: Yamakage M, Hirshman CA, Croxton TL.
    Journal: Anesthesiology; 1995 Dec; 83(6):1274-82. PubMed ID: 8533920.
    Abstract:
    BACKGROUND: Intravenously administered anesthetics directly inhibit airway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smooth muscle requires the influx of Ca2+ through voltage-dependent Ca2+ channels, it was hypothesized that intravenous anesthetics inhibit airway smooth muscle voltage-dependent Ca2+ channels. METHODS: Porcine tracheal smooth muscle cells were enzymatically dispersed and studied using whole-cell, patch-clamp techniques. The cells were exposed to thiopental (10(-7)-3 x 10(-4) M), ketamine (10(-6)-10(-3) M), or propofol (10(-7)-3 x 10(-4) M) while recording macroscopic voltage-activated Ca2+ currents (ICa). RESULTS: Each intravenous anesthetic tested significantly inhibited ICa in a dose-dependent manner with 3 x 10(-4) M thiopental, 10(-3) M ketamine, and 3 x 10(-4) M propofol each causing approximately 50% depression of peak ICa, but with no apparent shift in the voltage dependence of induced ICa. After pretreatment with the Ca2+ channel agonist Bay K 8644, thiopental, but not ketamine or propofol, shifted the maximum ICa to more positive potentials. All three anesthetics promoted the inactivated state of the channel at more negative potentials, but propofol was less effective than thiopental or ketamine in this regard. CONCLUSIONS: Three intravenous anesthetics evaluated in this study decreased the ICa of porcine tracheal smooth muscle cells but with subtle electrophysiologic differences. Hence, thiopental, ketamine, and propofol each inhibit L-type voltage-dependent Ca2+ channels of porcine tracheal smooth muscle cells but the molecular mechanisms involved may be agent specific. This inhibition may contribute to the airway smooth muscle relaxant effects of these agents observed in vitro at concentrations greater than those encountered clinically.
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