Abstract
Hydrogen peroxide (H&sub2;O&sub2;) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H&sub2;O&sub2; is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H&sub2;O&sub2; modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10-500 μM H&sub2;O&sub2;. However, 500 μM H&sub2;O&sub2; modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance (R(i)), hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H&sub2;O&sub2; increased conductance of barium-sensitive potassium currents, and block of these currents ablated H&sub2;O&sub2;-induced changes in RMP, Ri and AP discharge. Following washout of H&sub2;O&sub2; AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H&sub2;O&sub2; exposure. H&sub2;O&sub2; effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H&sub2;O&sub2; initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes.