Inhibitory Signaling to Ion Channels in Hippocampal Neurons Is Differentially Regulated by Alternative Macromolecular Complexes of RGS7

• DOI: 10.1523/jneurosci.1378-18.2018
• Publication Date: 2018-10-12T18:35:17Z
• Authors: Olga I. Ostrovskaya; Cesare Orlandi; Ana Fajardo-Serrano; Samuel M. Young; Rafael Lujan; Kirill A. Martemy...
• Keywords: Male; Mice, Knockout; Neurons; 0301 basic medicine; Insecta; Caveolin 2; Neural Inhibition; Hippocampus; Ion Channels; Mice; 03 medical and health sciences; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Animals; Female; Cells, Cultured; RGS Proteins; Signal Transduction

The neuromodulatory effects of GABA on pyramidal neurons are mediated by B receptors (GABA Rs) that signal via a conserved G-protein-coupled pathway. Two prominent effectors regulated Rs include G-protein inwardly rectifying K + (GIRK) and P/Q/N type voltage-gated Ca 2+ (Ca V 2) ion channels control excitability synaptic output these neurons, respectively. Regulator signaling 7 (RGS7) has been shown to effects, yet the specificity its impacts effector underlying molecular mechanisms is poorly understood. In this study, we show hippocampal RGS7 forms two distinct complexes with alternative subunit configuration bound either membrane protein R7BP (RGS7 binding protein) or orphan receptor GPR158. Quantitative biochemical experiments both account for targeting nearly entire pool plasma membrane. We analyzed effect genetic elimination in mice sexes overexpression various components complex patch-clamp electrophysiology cultured brain slices. report prominently regulates R 2, addition known involvement modulating GIRK. Strikingly, only containing R7BP, but not GPR158, accelerated kinetics GIRK 2 modulation Rs. contrast, GPR158 exerted opposite inhibited RGS7-assisted temporal GABA. Collectively, our data reveal which distinctly composed macromolecular modulate activity key mediate inhibitory CA1 neurons. SIGNIFICANCE STATEMENT This study identifies contributions major regulator controlling channel function implications understanding plasticity, learning, memory.