Functional Properties of AMPA and NMDA Receptors Expressed in Identified Types of Basal Ganglia Neurons

Abstract

AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs) mediate excitatory synaptic transmission in the basal ganglia and may contribute to excitotoxic injury. We investigated the functional properties of AMPARs and NMDARs expressed by six main types of basal ganglia neurons in acute rat brain slices (principal neurons and cholinergic interneurons of striatum, GABAergic and dopaminergic neurons of substantia nigra, globus pallidus neurons, and subthalamic nucleus neurons) using fast application of glutamate to nucleated and outside-out membrane patches. AMPARs in different types of basal ganglia neurons were functionally distinct. Those expressed in striatal principal neurons exhibited the slowest gating (desensitization time constant τ = 11.5 msec, 1 m m glutamate, 22°C), whereas those in striatal cholinergic interneurons showed the fastest gating (desensitization time constant τ = 3.6 msec). The lowest Ca 2+permeability of AMPARs was observed in nigral dopaminergic neurons (PCa/PNa= 0.10), whereas the highest Ca 2+permeability was found in subthalamic nucleus neurons (PCa/PNa= 1.17). NMDARs of different types of basal ganglia neurons were less variable in their functional properties; those expressed in nigral dopaminergic neurons exhibited the slowest gating (deactivation time constant of predominant fast component τ 1= 150 msec, 100 μ m glutamate), and those of globus pallidus neurons showed the fastest gating (τ 1= 67 msec). The Mg 2+block of NMDARs was similar; the average chord conductance ratio g−60mV/g+40mV was 0.18–0.22 in 100 μ m external Mg 2+. Hence, AMPARs expressed in different types of basal ganglia neurons are markedly diverse, whereas NMDARs are less variable in functional properties that are relevant for excitatory synaptic transmission and neuronal vulnerability.