Tonic GluD1 channel current is independent of G protein activity in the dorsal raphe nucleus

Abstract

AbstractPreviously, using electrophysiological recordings from adult male and female mouse brain slices containing the dorsal raphe nucleus, we showed that GluD1R channels carry ionic current and are modulated via activation of Gαq-coupled α1-adrenergic receptors (α1-AR) in a GTP-dependent manner (Gantz et al., 2020). GluD1R channels also carry a tonic cation current, generally ~−20 pA at subthreshold membrane potentials (Gantz et al., 2020). The origin of tonic GluD1R channel current is unknown. Here, using the same preparation, we show there is no role of on-going G protein-coupled receptor activity in generating or sustaining tonic GluD1R channel current. Neither augmentation nor disruption of G protein activity had an effect on tonic GluD1R current. These results reveal that tonic GluD1R current arises from a mechanism separate from on-going activity of G protein-coupled receptors. Under current clamp, block of GluD1R channels hyperpolarized the membrane by ~10 mV at subthreshold potentials leading to reduced excitability. Thus, GluD1R channels carry a G protein-independent tonic current that contributes to subthreshold drive of action potential firing in the dorsal raphe nucleus.