Ketamine is a frequently used intravenous anesthetic, which can reversibly induce loss of consciousness (LOC). Previous studies have demonstrated that thalamocortical system is critical for information transmission and integration in the brain. The ventral posteromedial nucleus (VPM) is a critical component of thalamocortical system. Glutamate is an important excitatory neurotransmitter in the brain and may be involved in ketamine-induced LOC. The study used whole-cell patch-clamp to observe the effect of ketamine (30 μM–1000 μM) on glutamatergic neurotransmission in VPM slices. Ketamine significantly decreased the amplitude of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs), but only higher concentration of ketamine (300 μM and 1000 μM) suppressed the frequency of sEPSCs. Ketamine (100 μM–1000 μM) also decreased the amplitude of glutamatergic miniature excitatory postsynaptic currents (mEPSCs), without altering the frequency. In VPM neurons, ketamine attenuates the glutamatergic neurotransmission mainly through postsynaptic mechanism and action potential may be involved in the process.

Ketamine is commonly used as a dissociative anesthetic with unique actions in the central nervous system. Previous studies have found that the thalamocortical systems play an important role in general anesthetics induced unconsciousness. Whether the voltage-gated sodium channels in the thalamocortical systems are the target of ketamine remain unclear. The present study used a whole-cell patch-clamp technique to observe the effects of ketamine on voltage-gated Na⁺ channels in thalamocortical pyramidal neurons. We found that IC50 of ketamine on Na⁺ currents in the primary somatosensory barrel cortex pyramidal neurons and the thalamus ventral posteromedial nucleus pyramidal neurons was 686.72 ± 39.92 and 842.65 ± 87.28 μM, respectively. Ketamine accelerated the Na⁺ channels inactivation and slowed inactivation of Na⁺ channels after recovery but did not affect the activation. We demonstrated the detailed suppression process of neural voltage-gated Na⁺ channels by ketamine on thalamocortical slice. This may provide a new insight into the mechanical explanation for the ketamine anesthesia.

Ketamine is an intravenous anesthetic commonly used in clinical, which has sedative and analgesic effects. Potassium channels exert many physiological functions in excitable cells. Therefore, potassium channels may be one of the targets of ketamine. In this study, we used patch clamp to study the effects of ketamine on voltage-gated potassium channels in primary sensory cortex (S1) neurons. We recorded the outward potassium currents (IA) and delayed rectifier potassium currents (IK) separately. We found that ketamine both concentration-dependently inhibited IA currents and IK currents in S1 neurons. Ketamine (100 and 300 mu M) induced a concentration-dependent hyperpolarizing shift in V-1/2, without affecting the slope factor (kappa) or inactivation of IA. Ketamine induced a concentration-dependent hyperpolarizing shift in V-1/2 of IK, without affecting its kappa. Ketamine (100 and 300 mu M) did not alter the steady-state activation or its kappa. Hence, ketamine inhibits IA and IK in a concentration-dependent manner in S1 pyramidal neurons. The inactivation of IA does not appear to be involved in the inhibitory effect of ketamine on IA. Ketamine inhibits IK mainly by speeding up the inactivation of IK in S1 pyramidal neurons.