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J Physiol Volume 586, Number 12, 2913-2926, June 15, 2008 DOI: 10.1113/jphysiol.2008.153437
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NEUROSCIENCE

Synaptic inhibition by glycine acting at a metabotropic receptor in tiger salamander retina

 Mingli Hou1, Lei Duan1 and Malcolm M. Slaughter1

1 Program in Neuroscience and Department of Physiology and Biophysics, State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY 14214, USA

Glycine is the lone fast neurotransmitter for which a metabotropic pathway has not been identified. In retina, we found a strychnine-insensitive glycine response in bipolar and ganglion cells. This glycine response reduced high voltage-activated calcium current. It was G-protein mediated and protein kinase A dependent. The EC50 of the metabotropic glycine response is 3 µM, an order of magnitude lower than the ionotropic glycine receptor in the same retina. The bipolar cell glutamatergic input to ganglion cells was suppressed by metabotropic glycine action. The synaptic output of about two-thirds of bipolar cells and calcium current in two-thirds of ganglion cells are sensitive to the action of glycine at metabotropic receptors, suggesting this signal regulates specific synaptic pathways in proximal retina. This study resolves the curious absence of a metabotropic glycine pathway in the nervous system and reveals that the major fast inhibitory neurotransmitters, GABA and glycine, both activate G-protein-coupled pathways as well.

(Received 4 March 2008; accepted after revision 17 April 2008; first published online 25 April 2008)
Corresponding author M. Hou: Department of Physiology and Biophysics, State University of New York at Buffalo, 124 Sherman Hall, 3435 Main Street, Buffalo, NY 14214, USA. Email: mingli_hou{at}hms.harvard.edu






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