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 (IK) upon depolarization. The H2O2 hyperpolarization was blocked by K+ channel blockers. H2O2 did not alter currents between -50 and -110 mV. However, H2O2 induced an outward IK at -50 mV yet, at potentials more positive to 0 mV H2O2, decreased IK. 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 IK, which may ultimately alter cardiorespiratory reflexes.