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Vol. 302, Issue 3, 1135-1145, September 2002
Department of Neuropharmacology, The Scripps Research Institute, La
Jolla, California
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 Ca2+-free, Ba2+-containing
solution, suggesting that the anionic conductance was not activated by
Ca2+ 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 µM picrotoxin and 10 µM zinc, was
weakly antagonized by 1 µM strychnine, and was not enhanced by
1 µM 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.
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