INHIBITORY EFFECTS OF THIOPENTAL KETAMINE, AND PROPOFOL ON VOLTAGE-DEPENDENT CA2-MUSCLE CELLS( CHANNELS IN PORCINE TRACHEAL SMOOTH)

Background: Intravenously administered anesthetics directly inhibit ai rway smooth muscle contraction. Because many anesthetic agents affect membrane ion channel function and sustained contraction of airway smoo th muscle requires the influx of Ca2+ through voltage-dependent Ca2+ c hannels, it was hypothesized that intravenous anesthetics inhibit airw ay smooth muscle voltage-dependent Ca2+ channels. Methods: Porcine tra cheal smooth muscle cells were enzymatically dispersed and studied usi ng whole-cell, patch-clamp techniques, The cells were exposed to thiop ental (10(-7) - 3 X 10(-4) M), ketamine (10(-6) - 10(-3) M), or propof ol (10(-7) - 3 X 10(-4) M) while recording macroscopic voltage-activat ed Ca2+ currents (I-Ca). Results: Each intravenous anesthetic tested s ignificantly inhibited (I-Ca) in a dose-dependent manner with 3 X 10(- 4) M thiopental, 10(-3) M ketamine, and 3 X 10(-4) M propofol each cau sing similar to 50% depression of peak I-Ca but with no apparent shift in the voltage dependence of induced I-Ca. After pretreatment with th e Ca2+ channel agonist Bay K 8644, thiopental but not ketamine or prop ofol, shifted the maximum I-Ca to more positive potentials. All three anesthetics promoted the inactivated state of the channel at more nega tive potentials, but propofol was less effective than thiopental or ke tamine in this regard. Conclusions: Three intravenous anesthetics eval uated in this study decreased the I-Ca of porcine tracheal smooth musc le cells but with subtle electrophysiologic differences. Hence, thiope ntal, ketamine, and propofol each inhibit L-type voltage-dependent Ca2 + channels of porcine tracheal smooth muscle cells but the molecular m echanisms involved may be agent specific. This inhibition may contribu te to the airway smooth muscle relaxant effects of these agents observ ed in vitro at concentrations greater than those encountered clinicall y.