Neuropeptide S Receptor Stimulation Excites Principal Neurons in Murine Basolateral Amygdala through a Calcium-Dependent Decrease in Membrane Potassium Conductance

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 (E-K) and was accompanied by an increase in membrane input resistance. GDP-beta-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, G(alpha q) signaling and calcium ions seem to be mandatory for the observed current and increased neuronal excitability.

Automated summary

The neuropeptide S system, consisting of the NPS and NPSR1, has been extensively studied in rodents. Activation of NPSR1 in amygdalar neurons inhibits voltage-gated potassium channels and increases neuronal excitability through G(alpha q) signaling and calcium ions.