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 μM cobalt reduced the sEPSC rate without affecting their peak amplitude, which is consistent with hyperpolarization or the suppression of Ca 2+ 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 a 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 μM), 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 μM (s)-2-methyl-2-amino-4-phosphonobutyrate (MAP4), a selective antagonist of group III mGluR, and with 200 μM 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 Ca 2+ conductance. These results suggest that the activation of group III mGluRs suppresses transmitter release from cone presynaptic terminals via a 4-AP–sensitive pathway. Negative feedback, operating via mGluR autoreceptors, may limit excessive glutamate release from cone synaptic terminals. EPSC L-APB horizontal cell mGluR photoreceptor cell Footnotes The present address of Dr. H. Hirasawa is Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan. Abbreviations used in this paper: 4-AP, 4-aminopyridine; CNQX, 6-cyano-7-nitroquinoxaline; HC, horizontal cell; L-APB or L-AP4, ( l )-2-amino-4-phosphonobutyric acid; mGluR, metabotropic glutamate receptor; sEPSC, spontaneous excitatory postsynaptic current. Submitted: 19 September 2001 Revision requested 19 November 2001 Accepted: 20 November 2001
The Journal of General Physiology – Rockefeller University Press
Published: Jan 1, 2002
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