In addition to numerous GABA-ergic efferent neurons, the striatum contains a subpopulation of fast-firing GABA-ergic interneurons characterized by the presence of immunoreactivity for the calcium-binding protein, parvalbumin. Double-label in situ hybridization with digoxigenin- and radiolabelled cRNA probes was performed on striatal sections of adult rats to identify mRNAs expressed by striatal GABA-ergic interneurons. In the dorsolateral striatum, only parvalbumin mRNA-positive neurons expressed the mRNA encoding the potassium channel Kv3.1, a member of the Shaw family of potassium channels with rapid activation and inactivation kinetics, usually found in fast-firing neurons such as the basket cells of the hippocampus. Colocalization of the parvalbumin and Kv3.1 proteins was confirmed by double-label immunohistochemistry. Parvalbumin mRNA-positive neurons expressed very high levels of the mRNA encoding glutamic acid decarboxylase (Mr 67,000: GAD67) in the dorsolateral striatum. A smaller proportion of double-labelled neurons was found in the ventrolateral striatum. A small number of densely labelled neurons for GAD67 mRNA also expressed the mRNA encoding the dopamine D2 receptor, but none expressed detectable levels of the dopamine D1 receptor mRNA. This indicates major differences in the expression of dopamine receptor mRNA in a majority of GABA-ergic interneurons vs. GABA-ergic efferent neurons of the striatum. The results suggest that distinct molecular characteristics are associated with the distinct electrophysiological properties of striatal GABA-ergic neurons.

Pharmacological and molecular biological evidence indicates the existence of multiple types of NMDA receptors within the CNS. We have characterized pharmacological properties of receptors assembled from the combination of NR 1a and NR 2B subunits (NR 1a/2B) expressed in transfected cells using both 125I‐MK‐801 binding assays and electrophysiological measures. Binding of 125I‐MK‐801 to cells transfected with NR 1a/2B is saturable with a KD of 440 pM. The binding is potently inhibited by ketamine, dextromethorphan, phencyclidine, and MK‐801 and is stimulated by low concentrations of magnesium. These properties resemble those of native receptors and receptors produced by NR 1a/2A. However, 125I‐MK‐801 binding to membranes from cells transfected with NR 1a/2B is inhibited with high affinity by ifenprodil and is stimulated by spermidine, unlike receptors assembled from NR 1a/2A. NMDA‐induced currents measured in cells transfected with either NR 1a/2A or NR 1a/2B have pharmacological properties that correlate well with the binding studies. Currents in cells transfected with NR 1a/2B are potentiated by spermidine and blocked with high affinity by ifenprodil, whereas currents in cells transfected with NR 1a/2A are not enhanced by spermidine and are weakly inhibited by ifenprodil. These data suggest that pharmacological heterogeneity in native NMDA receptors may be explained by combinations of different subunits.

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