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 HO 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 HO 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, HO hyperpolarized PVN neurons and decreased action potential discharge. In the slice preparation, HO also decreased spontaneous excitatory postsynaptic current frequency, but not amplitude. To examine potential mechanisms, we investigated the influence of the K channel blockers Ba, Cs, and glibenclamide on membrane potential, as well as the ionic currents active at resting potential and outward K currents () upon depolarization. The HO hyperpolarization was blocked by K channel blockers. HO did not alter currents between -50 and -110 mV. However, HO induced an outward at -50 mV yet, at potentials more positive to 0 mV HO, decreased . Elevated intracellular antioxidant catalase eliminated HO effects. These data indicate that HO alters synaptic and neuronal properties of PVN neurons likely via membrane hyperpolarization and alteration of , which may ultimately alter cardiorespiratory reflexes.