Potentiation of neuronal activity by tonic GluD1 current in brain slices.

Ion channel function of native delta glutamate receptors (GluDR) is incompletely understood. Previously, we and others have shown that activation of Gαq protein‐coupled receptors (GqPCR) produces a slow inward current carried by GluD1R. GluD1R also carries a tonic cation current of unknown cause. Here, using voltage‐clamp electrophysiological recordings from adult mouse brain slices containing the dorsal raphe nucleus, we find no role of ongoing G‐protein‐coupled receptor activity in generating or sustaining tonic GluD1R currents. Neither augmentation nor disruption of G protein activity affects tonic GluD1R currents, suggesting that ongoing G‐protein‐coupled receptor activity does not give rise to tonic GluD1R currents. Further, the tonic GluD1R current is unaffected by the addition of external glycine or D‐serine, which influences GluD2R current at millimolar concentrations. Instead, GqPCR‐stimulated and tonic GluD1R currents are regulated by physiological levels of external calcium. In current‐clamp recordings, block of GluD1R channels hyperpolarizes the membrane by ~7 mV at subthreshold potentials, reducing excitability. Thus, GluD1R carries a G‐protein‐independent tonic current that contributes to subthreshold neuronal excitation in the dorsal raphe nucleus. Synopsis: GluD1 receptors localize at synapses in nearly every brain region but their function as an ion channel remains poorly understood. This study reveals a tonic "standing" current carried by GluD1 receptors in neurons that promotes action potential firing. Tonic GluD1R current is not a product of GPCR activity, nor ambient glycine.GluD1R current is inhibited by external calcium, in a manner similar to magnesium block of GluNR.Even though tonic GluD1 current is small, it does potentiate neuronal excitability. It contributes to subthreshold depolarization and action potential firing in dorsal raphe serotonin neurons. [ABSTRACT FROM AUTHOR]