No abstract

The 50% effective concentration for loss of righting reflex and MAC values for the volatile anesthetics were not altered after alpha1G calcium channel knockout, indicating that normal functioning of alpha1G calcium channels is not required for the maintenance of anesthetic hypnosis and immobility. However, the timely induction of anesthesia/hypnosis by volatile anesthetic agents and some intravenous anesthetic agents may require the normal functioning of these channel subunits.

Ketamine is an IV anesthetic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine. Here, we evaluated a righting reflex to determine the general anesthetic/hypnotic potency of ketamine administered intraperitoneally to GluRepsilon1 knockout mice and compared these results with those for wild-type mice. Mutant mice were more resistant to ketamine than control mice. Unexpectedly, mutant mice were also more resistant to pentobarbital, which is thought not to interact with NMDAR at clinically relevant concentrations. Although these data in no way eliminate the possibility of the involvement of the NMDAR GluRepsilon1 subunit in mediation of ketamine anesthesia/hypnosis, they suggest the difficulties with interpretation of altered anesthetic sensitivity in knockout animal models.

The N-methyl-D-aspartate (NMDA) receptor NR3B subunit co-assembles with NR1 and NR2 subunits to form a receptor complex with distinct channel properties. In the present study, we investigated the effects of co-expression of the NR3B subunit on the anesthetic sensitivities of NMDA receptors for NR1/NR2 channels expressed in Xenopus oocytes. Although the NR3B subunit prominently reduced the current amplitude of NR1/NR2A-B channels, the sensitivities of NR1/NR2A-B channels to Mg2+, ketamine, isoflurane, nitrous oxide, and ethanol were not altered by coexpression of the NR3B subunit. These results suggest that the anesthetic sensitivities of NMDA receptors do not depend on the presence or absence of the NR3 subunit. Mutations of two amino acid residues in the NR3B subunit at positions homologous to the N and N + 1 sites in the NR1 and NR2 subunits, which constitute the blocking sites for Mg2+ and ketamine, did not affect the sensitivities of NR1/NR2B/NR3B channels to Mg2+, ketamine and isoflurane. Thus, the amino acid residues at the N and N + 1 sites in NR3 subunits are unlikely to be involved in the formation of channel blocking sites in NR1/NR2/NR3 channels.

Taurine has been suggested to modulate nociceptive information at the spinal cord level. In this study, the pharmacological properties of taurine were investigated in adult rat substantia gelatinosa (SG) neurons using whole-cell patch-clamp method. We found that taurine seemed to have higher efficacy than glycine on glycine receptors in SG neurons. An increase in chloride conductance was responsible for taurine-induced currents. Taurine at 0.3 mM activated glycine receptors, whereas at 3 mM activated both glycine and gamma-aminobutyric acid A receptors. The currents activated by coapplication of taurine and glycine are cross inhibitive. Altogether these results show that taurine might represent another important neurotransmitter or modulator in SG neurons, which may be involved in antinociception.