Abstract
Background: The neuropeptide S system, consisting of the 20 amino acid neuropeptide NPS and its G-protein-coupled receptor (GPCR) neuropeptide S receptor 1 (NPSR1), has been studied intensively in rodents. Although there is a lot of data retrieved from behavioral studies using pharmacology or genetic interventions, little is known about intracellular signaling cascades in neurons endogenously expressing the NPSR1. Methods: To elucidate possible G-protein-dependent signaling and effector systems, we performed whole-cell patch-clamp recordings on principal neurons of the anterior basolateral amygdala of mice. We used pharmacological interventions to characterize the NPSR1-mediated current induced by NPS application. Results: Application of NPS reliably evokes inward-directed currents in amygdalar neurons recorded in brain slice preparations of male and female mice. The NPSR1-mediated current had a reversal potential near the potassium reversal potential (EK) and was accompanied by an increase in membrane input resistance. GDP-β-S and BAPTA, but neither adenylyl cyclase inhibition nor 8-Br-cAMP, abolished the current. Intracellular tetraethylammonium or 4-aminopyridine reduced the NPS-evoked current. Conclusion: NPSR1 activation in amygdalar neurons inhibits voltage-gated potassium (K+) channels, most likely members of the delayed rectifier family. Intracellularly, Gαq signaling and calcium ions seem to be mandatory for the observed current and increased neuronal excitability.
Highlights
The neuropeptide S system, consisting of the 20 amino acid neuropeptide NPS and itsG-protein-coupled receptor (GPCR) neuropeptide S receptor 1 (NPSR1) has been identified in the central nervous system of rodents and humans [1,2]
The vast majority of available studies describe the function of the NPS system on a network level [8,22], analyze behavioral consequences following pharmacological or genetic interventions [5,9,31], or point out implications of NPSR1 single-nucleotide polymorphisms for psychiatric disorders in humans [32,33]
We can (a) confirm the expression profile of NPSR1 mRNA in the anterior part of the basolateral amygdala (aBA), (b) describe NPS-specific activation of the NPSR1 in aBA principal neurons (PN) of male and female mice, (c) provide evidence that the NPSR1mediated inward current is dependent on Gαq signaling, (d) identify a reduction of membrane K+ conductance in these neurons as consequence of NPSR1 stimulation, and (e) show NPS-induced increase in neuronal excitability
Summary
G-protein-coupled receptor (GPCR) neuropeptide S receptor 1 (NPSR1) has been identified in the central nervous system of rodents and humans [1,2]. NPS and its G-protein-coupled receptor (GPCR) neuropeptide S receptor 1 (NPSR1), has been studied intensively in rodents. There is a lot of data retrieved from behavioral studies using pharmacology or genetic interventions, little is known about intracellular signaling cascades in neurons endogenously expressing the NPSR1. Methods: To elucidate possible G-protein-dependent signaling and effector systems, we performed whole-cell patch-clamp recordings on principal neurons of the anterior basolateral amygdala of mice. We used pharmacological interventions to characterize the NPSR1-mediated current induced by NPS application. Results: Application of NPS reliably evokes inward-directed currents in amygdalar neurons recorded in brain slice preparations of male and female mice. Gαq signaling and calcium ions seem to be mandatory for the observed current and increased neuronal excitability
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