The general anesthetic pentobarbital slows desensitization and deactivation of the glycine receptor in the rat spinal dorsal horn neurons.
Although many general anesthetics have been found to produce anesthetic and analgesic effects by augmenting GABA(A) receptor (GABA(A)R) function, the role of the glycine receptor (GlyR) in this process is not fully understood at the neuronal level in the spinal cord. We investigated the effects of a barbiturate general anesthetic, pentobarbital (PB), on the glycinergic miniature inhibitory postsynaptic currents (mIPSCs) and the responses to exogenously applied glycine, or taurine, a low affinity GlyR agonist, by using the whole-cell patch-clamp technique in the rat spinal dorsal horn neurons isolated using a novel mechanical method. Bath application of 30 microm PB significantly prolonged the decay time constant of the spontaneous glycinergic mIPSC without changing its amplitude and frequency. Co-application of 0.3 mm PB reduced the peak amplitude, affected the macroscopic desensitization and deactivation of the response to externally applied Gly in a concentration-dependent manner. In addition, the recovery of Gly response from desensitization was also prolonged by PB. However, PB did not change the desensitization and deactivation kinetics of the taurine-induced response. The GABA(A)R antagonist bicuculline (10 microm) did not affect the effect of PB on the Gly response. Thus, PB prolonged the spinal glycinergic mIPSCs by slowing desensitization and deactivation of GlyR. Two other structurally different intravenous anesthetics, i.e. propofol (10 microm) and etomidate (3 microm), prolonged the duration of the glycinergic mIPSC in the rat spinal dorsal horn neurons. In conclusion, on GlyR-Cl(-) channel complexes there may exist action site(s) of intravenous general anesthetics. GlyR and glycinergic neurotransmission may play an important role in the modulation of general anesthesia in the mammalian spinal cord.
Lu
Hui
H
Laboratory of Receptor Pharmacology, Department of Neurobiology and Biophysics, University of Science and Technology of China, Hefei 230027, People's Republic of China.
Xu
Tian-Le
TL
D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D005045:Etomidate / Q000494:pharmacology; D009433:Neural Inhibition; D010424:Pentobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D018009:Receptors, Glycine / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013654:Taurine / Q000494:pharmacology
D018681:Anesthetics, General; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D013654:Taurine; D010424:Pentobarbital; D015742:Propofol; D005045:Etomidate