Electrophysiological evidence for expression of glycine receptors in freshly isolated neurons from nucleus accumbens.
In the course of studying N-methyl-D-aspartate (NMDA) receptors of the nucleus accumbens (NAcc), we found that 20% of freshly isolated medium spiny neurons, as well as all interneurons, responded in an unexpected way to long (5-s) coapplication of NMDA and glycine, the coagonist of NMDA receptors. Whereas the reversal potential of the peak NMDA current of this subset of neurons was still around 0 mV, the desensitizing current became outward at hyperpolarized potentials around -30 mV. A Cl(-)-free solution shifted the equilibrium potentials of the desensitized currents to around 0 mV. This outward current was not blocked by a Ca(2+)-free, Ba(2+)-containing solution, suggesting that the anionic conductance was not activated by Ca(2+) influx through NMDA receptor channels. Interestingly, glycine alone also evoked a current with a similar hyperpolarized reversal potential in this subset of neurons. The glycine current reversed around -50 mV, rectified outwardly, and inactivated strongly. Its desensitization was best fitted with a double exponential. Only the slow desensitization showed clear voltage dependence. The glycine current was not blocked by 200 microM picrotoxin and 10 microM zinc, was weakly antagonized by 1 microM strychnine, and was not enhanced by 1 microM zinc. In addition, 1 mM taurine, but not GABA, inactivated glycine currents, and 1 mM glycine occluded 10 mM taurine-mediated currents. These data indicate that a subset of nucleus accumbens neurons expresses glycine receptors and that either glycine or taurine could be an endogenous agonist for these receptors.
Martin
Gilles
G
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA. gilles.martin@umassmed.edu
Siggins
George Robert
GR
D000818:Animals; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013331:Strychnine / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D018755:GABA Agonists; D005998:Glycine; D018684:Glycine Agents; D016202:N-Methylaspartate; D010852:Picrotoxin; D018009:Receptors, Glycine; D013331:Strychnine; D015032:Zinc