Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters

EXCITATORY amino acids mediate fast synaptic transmission in the central nervous system through the activation of at least three distinct ionotropic receptors: N-methyl-D-aspartate (NMDA), the α-amino-3-hydroxy-5-methyl-isoxasole-4-propionate(AMPA)/ quisqualate (QUIS) and the kainate subtypes (for reviews, see refs 1, 2). They also activate the additional QUIS 'metabotropic' receptor (sensitive to trans-l-amino-cyclopentyl-l,3-dicarboxylate, ACPD) linked to inositol phospholipid metabolism^3-5. We have used hippocampal slice cultures to study the electrophysio-logical consequences of the metabotropic response. We find that activation of an ACPD-sensitive QUIS receptor produces a 'slow' excitation of CA3 pyramidal cells, resulting from depression of a Ca²⁺-dependent K⁺ current and a voltage-gated K⁺ current. Combined voltage-clamp and microfluorometric recordings show that, although these receptors can trigger an increase in intracellular Ca²⁺ concentration^6-8, suppression of K⁺ currents is independent of changes in intracellular Ca²⁺. These effects closely resemble those induced by activating muscarinic acetylcholine receptors in the same neurons and suggest that excitatory amino acids not only act as fast ionotropic transmitters but also as slow neuromodulatory transmitters.