Hydrogen peroxide inhibits neurons in the paraventricular nucleus of the hypothalamus via potassium channel activation

The paraventricular nucleus (PVN) of the hypothalamus is an important homeostatic and reflex center for neuroendocrine, respiratory, and autonomic regulation, including during hypoxic stressor challenges. Such challenges increase reactive oxygen species (ROS) to modulate synaptic, neuronal, and ion channel activity. Previously, in the nucleus tractus solitarius, another cardiorespiratory nucleus, we showed that the ROS H₂O₂ induced membrane hyperpolarization and reduced action potential discharge via increased K⁺ conductance at the resting potential. Here, we sought to determine the homogeneity of influence and mechanism of action of H₂O₂ on PVN neurons. We recorded PVN neurons in isolation and in an acute slice preparation, which leaves neurons in their semi-intact network. Regardless of preparation, H₂O₂ hyperpolarized PVN neurons and decreased action potential discharge. In the slice preparation, H₂O₂ also decreased spontaneous excitatory postsynaptic current frequency, but not amplitude. To examine potential mechanisms, we investigated the influence of the K⁺ channel blockers Ba²⁺,Cs⁺, and glibenclamide on membrane potential, as well as the ionic currents active at resting potential and outward K⁺ currents (I_K) upon depo-larization. The H₂O₂ hyperpolarization was blocked by K⁺ channel blockers. H₂O₂ did not alter currents between <50 and <110 mV. However, H₂O₂ induced an outward I_K at <50 mV yet, at potentials more positive to 0 mV H₂O₂, decreased I_K. Elevated intracellular antioxidant catalase eliminated H₂O₂ effects. These data indicate that H₂O₂ alters synaptic and neuronal properties of PVN neurons likely via membrane hyperpolarization and alteration of I_K, which may ultimately alter cardiorespiratory reflexes.