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

Ion channel function of native delta glutamate receptors (GluD R ) is incompletely understood. Previously, we and others have shown that activation of Gαq protein-coupled receptors (GqPCR) produces a slow inward current carried by GluD1 R . GluD1 R 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 GluD1 R currents. Neither augmentation nor disruption of G protein activity affects tonic GluD1 R currents, suggesting that ongoing G-protein-coupled receptor activity does not give rise to tonic GluD1 R currents. Further, the tonic GluD1 R current is unaffected by the addition of external glycine or D-serine, which influences GluD2 R current at millimolar concentrations. Instead, GqPCR-stimulated and tonic GluD1 R currents are regulated by physiological levels of external calcium. In current-clamp recordings, block of GluD1 R channels hyperpolarizes the membrane by ~7 mV at subthreshold potentials, reducing excitability. Thus, GluD1 R carries a G-protein-independent tonic current that contributes to subthreshold neuronal excitation in the dorsal raphe nucleus.