Neuropeptide W has bidirectional effects on the membrane potential of arcuate nucleus neurons

Abstract

The previously orphaned receptor GPR7 and its endogenous ligand neuropeptide W (NPW) are found in the hypothalamic arcuate nucleus. Therefore, they have the potential to modulate a variety of autonomic processes via interaction with the neurons in this nucleus. Using a combination of whole cell patch clamp recording from hypothalamic brain slices containing the arcuate nucleus and single-cell reverse transcriptase polymerase chain reaction we have characterized the response of arcuate neurons to NPW and identified the phenotypes of responsive cells. Neurons expressing somatostatin, neuropeptide Y and POMC depolarized when exposed to nanomolar concentrations of NPW during current clamp recordings. This depolarization was often followed by a slowly developing membrane hyperpolarization. A minority of neurons hyperpolarized in the absence of depolarization. When arcuate neurons were pre-treated with the voltage-gated sodium channel blocker TTX, the depolarizing effect of NPW was largely inhibited while the slowly developing hyperpolarization was preserved. Consequently, NPW appears to have two main actions on neurons in the arcuate nucleus. Firstly, a rapidly induced release of excitatory neurotransmitter onto these neurons, followed, secondly, with a long-lasting hyperpolarization to ensure the depolarization is terminated with prolonged NPW exposure.