RT Journal Article
SR Electronic
T1 L-AP4 inhibits calcium currents and synaptic transmission via a G- protein-coupled glutamate receptor
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2043
OP 2050
DO 10.1523/JNEUROSCI.12-06-02043.1992
VO 12
IS 6
A1 PQ Trombley
A1 GL Westbrook
YR 1992
UL http://www.jneurosci.org/content/12/6/2043.abstract
AB 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.