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Journal of Neuroscience, Vol 12, 2043-2050, Copyright © 1992 by Society for Neuroscience
L-AP4 inhibits calcium currents and synaptic transmission via a G- protein-coupled glutamate receptor
PQ Trombley and GL Westbrook
Department of Biology, University of Oregon, Eugene 97403.
The AP4 (2-amino-4-phosphonobutyrate) receptor is a presynaptic glutamate
receptor that inhibits transmitter release via an unknown mechanism. We
examined the action of L-AP4 on voltage-dependent calcium currents and
excitatory synaptic transmission on cultured olfactory bulb neurons using
whole-cell voltage-clamp methods. In neurons dialyzed with GTP, L-AP4
inhibited high-threshold calcium currents evoked in barium solutions. The
inhibition was irreversible in the presence of GTP-gamma-S and blocked by
removing intracellular Mg2+ or by preincubation with pertussis toxin (PTX),
consistent with the involvement of a PTX-sensitive G-protein. Dialysis with
staurosporine or buffering of intracellular calcium to pCa less than 8 did
not block the action of L-AP4, suggesting that protein phosphorylation or
release of intracellular calcium stores was not involved in calcium current
inhibition under these experimental conditions. PTX also blocked the L-
AP4-induced inhibition of monosynaptic EPSPs evoked by intracellular
stimulation of cultured mitral cells. These results suggest that the
presynaptic AP4 receptor is a G-protein-coupled glutamate receptor, and
that inhibition of calcium influx by a membrane-delimited action of a G-
protein may account for L-AP4-induced presynaptic inhibition.
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