Insensitivity of P- Type Calcium Channels to Inhalational and Intravenous General Anesthetics


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Abstract

BackgroundVoltage-gated Ca2+ channels long have been considered plausible targets for general anesthetics. Previous anesthetic studies have focused on L-, T-, or N-type channels, but there have been no studies on channels identified as P-type. Since P-type channels may be the most important voltage-gated Ca2+ channels involved in synaptic transmission in mammalian brain, it is important to establish their sensitivity to clinically relevant concentrations of general anesthetics.MethodsAcutely dissociated cerebellar Purkinje neurons were obtained from 7–14-day-old Sprague-Dawley rats. P-type currents were measured using the whole-cell version of the patch-clamp technique, with Ba2+ as the current carrier. General anesthetics were applied to the neurons in aqueous solution at room temperature (20–23°C).ResultsP-type Ca2+ channels were found to be very insensitive to a variety of general anesthetics and ethanol. Inhibitions of less than 10% were produced by 0.35 mM halothane, 0.35 μM isoflurane, 32 μM thiopental, 50 μM pentobarbital, 2 μM propofol, and 200 μM ethanol. Substantial anesthetic inhibition was found only at free aqueous concentrations much greater than those that are clinically relevant. For halothane, the dose-response curve showed an IC50 concentration of 1.17 ± 0.02 mM and a Hill coefficient of 2.02 ± 0.04 (mean ± SEM).ConclusionsThe relatively small Inhibitions of P-type Ca2+ channels produced by volatile and Intravenous anesthetics at their free aqueous EC50 concentrations for general anesthesia in mammals suggest that these channels do not play a major role in the induction of general anesthesia.

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