A metabotropic glutamate receptor regulates transmitter release from cone presynaptic terminals in carp retinal slices

The role of group III metabotropic glutamate receptors (mGluRs) in photoreceptor-H1 horizontal cell (HC) synaptic transmission was investigated by analyzing the rate of occurrence and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in H1 HCs uncoupled by dopamine in carp retinal slices. Red light steps or the application of 100 muM cobalt reduced the sEPSC rate without affecting their peak amplitude, which is consistent with hyperpolarization or the suppression of Ca2+ entry into cone synaptic terminals reducing vesicular transmitter release. Conversely, postsynaptic blockade of H1 HC AMPA receptors by 500 nM CNQX reduced the amplitude of sEPSCs without affecting their rate. This analysis of sEPSCs represents it novel methodology for distinguishing between presynaptic and postsynaptic sites of action, The selective agonist for group III mGluRs. L-2-amino-4-phosphonobutyrate (L-APB or L-AP4; 20 muM), reduced the sEPSC rate with a slight reduction in amplitude, which is consistent with a presynaptic action on cone synaptic terminals to reduce transmitter release. During L-APB application, recovery of sEPSC rate occurred with 500 muM (s)-2-methyl-2-amino-4-phosphonobutyrate (MAP4), a selective antagonist Of group III mGluR, and with 200 muM 4-aminopyridine (4-AP), a blocker of Voltage-dependent potassium channels. Whole-cell recordings from cones in the retinal slice showed no effect of L-APB on voltage-activated Ca2+ conductance. These results suggest that the activation of group III mGluRs suppresses transmitter release front cone presynaptic terminals via a 4-AP-sensitive pathway. Negative feedback, operating,via mGluR autoreceptors, may limit excessive glutamate release from cone synaptic terminals.