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

•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

SummaryG 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.