Effects of ketamine and propofol on P2X receptors in dorsal root ganglion neurons of the rat

Ketamine and propofol are widely used anesthetics in clinical practice. Ketamine is known to block the glutamate receptor channel of the N-methyl-D-aspartate (NMDA) type, resulting in suppression of an excitatory neurotransmission in the central nervous system. It is widely accepted that propofol enhances the inhibitory transmission mediated by γ-amino butyric acid (GABA). Recently, P2X receptors have been reported as possible targets for general anesthetics. However, the influences of ketamine and propofol are controversial. In the present study, we investigated the effects of ketamine and propofol on the ATP-induced currents in dorsal root ganglion (DRG) neurons of the rat using patch clamp technique. Wister rats of 10∼14 days old were decapitated with a lethal dose of pentobarbital sodium. DRG were rapidly dissected and kept in an incubation medium containing 2,000 U/ml Dispase for 30 min at 31°C. Thereafter, DRG neurons were dissociated mechanically with a fire-polished glass pipette. Electrical measurements were performed using the nystatin-perforated patch recording mode at a holding potential of -60 mV. Drugs were applied rapidly to the neurons using the Y-tube method. The ATP (1 μM)-induced current was divided into three types: fast desensitizing (fast type), slow desensitizing (slow type), and mixed of both types. To determine which subtype of P2X receptors were responsible for the fast and slow types, the effects of suramin, α, β-methylene ATP and β, γ-methylene ATP were tested. The fast type was attributed to activation of the P2X₃ subtype of the receptor, and the slow type was ascribed to activation of the P2X₂ subtype. Ketamine did not affect the ATP response of either type (Fig. 1). Propofol suppressed the peak current of the fast type dose-dependently (Fig. 2). On the other hand, in the slow type (Fig. 3), the peak current was not affected by propofol, but the decay in the presence of ATP was accelerated by the agent in a dose-dependent manner. In conclusion P2X receptors may not be involved in ketamine anesthesia or analgesia. The reduction in the P2X receptors by propofol may play a role in anesthesia by the agent, because a high concentration has been reported following intravenous administration of the agent. Further studies are needed to estimate the significance of P2X receptors in general anesthesia.