ANG II-induced excitation of paraventricular nucleus magnocellular neurons: a role for glutamate interneurons

The hypothalamic paraventricular nucleus (PVN) plays a critical role in cardiovascular and neuroendocrine regulation. ANG II (ANG) acts throughout the periphery in the maintenance of fluid-electrolyte homeostasis and has also been demonstrated to act as a neurotransmitter in PVN exerting considerable influence on neuronal excitability in this nucleus. The mechanisms underlying the ANG-mediated excitation of PVN magnocellular neurons have yet to be determined. We have used whole cell patch-clamp techniques in hypothalamic slices to examine the effects of ANG on magnocellular neurons. Application of ANG resulted in a depolarization of magnocellular neurons, a response that was abolished in TTX, suggesting an indirect mechanism of action. Interestingly, ANG also increased the frequency of excitatory postsynaptic potentials/currents in magnocellular neurons, an effect that was abolished after application of the glutamate antagonist kynurenic acid. ANG was without effect on the amplitude of excitatory postsynaptic currents, suggesting a presynaptic action on an excitatory interneuron within PVN. The ANG-induced depolarization was shown to be sensitive to kynurenic acid, revealing the requisite role of glutamate in mediating the ANG-induced excitation of magnocellular neurons. These observations indicate that the ANGergic excitation of magnocellular PVN neurons are dependent on an increase in glutamatergic input and thus highlight the importance of a glutamate interneuron in mediating the effects of this neurotransmitter.