| First Author | Philippart F | Year | 2018 |
| Journal | Elife | Volume | 7 |
| PubMed ID | 30556810 | Mgi Jnum | J:271472 |
| Mgi Id | MGI:6279720 | Doi | 10.7554/eLife.40984 |
| Citation | Philippart F, et al. (2018) Gi/o protein-coupled receptors in dopamine neurons inhibit the sodium leak channel NALCN. Elife 7:e40984 |
| abstractText | Dopamine (D2) receptors provide autoinhibitory feedback onto dopamine neurons through well-known interactions with voltage-gated calcium channels and G protein-coupled inwardly-rectifying potassium (GIRK) channels. Here, we reveal a third major effector involved in D2R modulation of dopaminergic neurons - the sodium leak channel, NALCN. We found that activation of D2 receptors robustly inhibits isolated sodium leak currents in wild-type mice but not in NALCN conditional knockout mice. Intracellular GDP-betaS abolished the inhibition, indicating a G protein-dependent signaling mechanism. The application of dopamine reliably slowed pacemaking even when GIRK channels were pharmacologically blocked. Furthermore, while spontaneous activity was observed in nearly all dopaminergic neurons in wild-type mice, neurons from NALCN knockouts were mainly silent. Both observations demonstrate the critical importance of NALCN for pacemaking in dopaminergic neurons. Finally, we show that GABA-B receptor activation also produces inhibition of NALCN-mediated currents. Therefore, we identify NALCN as a core effector of inhibitory G protein-coupled receptors. |
