Spontaneous Inhibitory Synaptic Currents Mediated by a G Protein-Coupled Receptor

• Published in: Neuron (Cambridge, Mass.) Vol. 78; no. 5; pp. 807 - 812
• Main Authors: Gantz, Stephanie C., Bunzow, James R., Williams, John T.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05-06-2013; Elsevier Limited
• Subjects: Analysis of Variance; Animals; Chelating Agents - pharmacology; Colforsin - pharmacology; Dopamine; Dopamine - metabolism; Dopamine Agents - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; Female; GABA Antagonists - pharmacology; Humans; In Vitro Techniques; Inhibitory Postsynaptic Potentials - drug effects; Inhibitory Postsynaptic Potentials - genetics; Inhibitory Postsynaptic Potentials - physiology; Levodopa - pharmacology; Male; Mesencephalon - cytology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Microscopy; Neurons; Neurons - drug effects; Neurons - physiology; Organophosphorus Compounds - pharmacology; Parkinson's disease; Patch-Clamp Techniques; Proteins; Receptors, Dopamine D2 - genetics; Receptors, G-Protein-Coupled - metabolism; Rodents; Serotonin Agents - pharmacology; Tyrosine 3-Monooxygenase - genetics
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.04.013

G protein-coupled receptors (GPCRs) affect many physiological processes by modulating both intrinsic membrane conductances and synaptic transmission. This study describes spontaneous miniature inhibitory postsynaptic currents mediated by vesicular dopamine release acting locally on metabotropic D2 receptors leading to the activation of a G protein-coupled inwardly rectifying potassium conductance. Thus, individual exocytotic events result in spontaneous GPCR-mediated transmission, similar to synaptic activation of classical ligand-gated ion channels.
•Spontaneous miniature GPCR/GIRK-dependent IPSCs were observed in dopamine neurons•Spontaneous IPSCs are not dependent on calcium entry or internal calcium stores•Spontaneous IPSCs are kinetically similar to electrically evoked IPSCs•Spontaneous IPSCs transiently inhibit pacemaker activity
Gantz et al. show that vesicular dopamine release produces spontaneous synaptic currents, mediated by D2 receptor activation of GIRK channels. Their findings demonstrate similarities between GPCR-mediated transmission and synaptic activation of classical ligand-gated ion channels.