Adropin Acts in the Paraventricular Nucleus of the Hypothalamus to Influence Neuronal Excitability
Adropin is a peptide hormone with cardiovascular and metabolic roles in the periphery, including effects on glucose and lipid homeostasis. Central administration of adropin has been shown to inhibit water intake in rats; however, the site at which central adropin acts has yet to be elucidated. The hypothalamic paraventricular nucleus (PVN), a critical autonomic control center, plays essential roles in the control of fluid balance, energy homeostasis and cardiovascular regulation, and is therefore a potential target for centrally-acting adropin. In the present study, we used whole- cell patch-clamp techniques to examine the effects of adropin on the excitability of neurons within the PVN. All three neuronal subpopulations (magnocellular, preautonomic, and neuroendocrine) in the PVN were found to be responsive to bath-application of 10 nM adropin, which elicited responses in 68% of cells tested (n = 57/84). The majority of cells (58%) depolarized (5.2 ± 0.3 mV; n = 49) in response to adropin, while the remaining responsive cells (10%) hyperpolarized (−3.4 ± 0.5 mV; n = 8), effects which were shown to be concentration-dependent. Additionally, responses were maintained in the presence of 1 μM tetrodotoxin in 75% of cells tested (n = 9/12), and voltage-clamp analysis revealed that adropin had no effect on the amplitude or frequency of excitatory or inhibitory postsynaptic currents (EPSCs and IPSCs) in PVN neurons, suggesting the peptide exerts direct, postsynaptic actions on these neurons. The electrophysiological effects of adropin on PVN neurons appear to be mediated partly by modulation of the transient potassium current. Collectively, these findings suggest central adropin may exert its physiological effects through direct actions on neurons in the PVN.