Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels

Biochemical and Biophysical Research Communications
Yun-Fei BaiZhi-Qing David Xu

Abstract

The noradrenergic neurons of the locus coeruleus (LC) are associated with various brain functions and psychiatric disorders, such as addiction and depression. It has been shown that neuropeptide galanin (GAL) inhibits neuronal excitability in LC, but the mechanisms remain unclear. In the present study, we investigated the ionic and signal transduction mechanisms underlying inhibitory effect of GAL on LC neurons using whole-cell patch clamp recording in rat brain slices. Bath application of GAL decreased the spontaneous firings and induced a dose-dependent hyperpolarization of LC neurons and this effect was attenuated by knockdown of Galr1, but not Galr2, confirming that mainly GALR1 mediates the inhibition effect of GAL. The inhibitory effect of GAL was also blocked by treatments of pertussis toxin (PTX), GTP-γ-s or GDP-β-s, respectively, indicating that the functions of PTX sensitive Gi/o protein are required for GAL-induced hyperpolarization. Moreover, the blockers of GIRK (tertiapin-Q or SCH2 3390 hydrochloride) attenuated the GAL response while blocker of BK/SK/KATP channels or TASK-1/3 channels did not affect it significantly, suggesting that GIRK channels play an important role in GAL-induced hyperpolarization in LC neuro...Continue Reading

Citations

Nov 11, 2019·Psychopharmacology·F MessanviY Chudasama
May 6, 2020·Biologics : Targets & Therapy·Desalegn Getnet DemsieAbere Tilahun Bantie
Jun 11, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yutao YangZhi-Qing David Xu

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