Hydrogen peroxide modulates barium‐sensitive K+‐currents of nucleus tractus solitarii neurons (686.14)

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The nTS holds a vital role in cardiorespiratory reflexes as the first central integration site of chemosensitive afferents. Hypoxia‐reoxygenation over‐produces H2O2, a potent neuromodulator and reactive oxygen species. We previously found in rat brainstem slices that second‐order nTS neurons initially reduce excitability when exposed to 500 µM H2O2. This was due to a reversible hyperpolarization in resting membrane potential (RMP; ‐10 mV) and reduction in membrane resistance (Ri; ‐224 MΩ). Since these effects occur at RMP (~ ‐60 mV), we determined the effect of H2O2 on K+ channel conductance using voltage steps and ramps between ‐100 and ‐50 mV in nTS slices. H2O2 increased the slope of holding currents during steps by 1.31 ±0.35 nS (N=6, p蠄0.01). Such currents reversed at ‐75 mV, indicating greater K+ conductance. Augmented conductance (+ 0.49 ±0.18 nS; N=5, p蠄0.05) by H2O2 was also observed during voltage ramps. Conductance changes persisted during blockade of glutamate and GABAA receptors, confirming such effects were not secondary to synaptic activation. H2O2‐induced alterations of RMP, Ri and slope conductance were eliminated by barium (100 µM), a blocker of inward rectifying (IRK) and 2‐pore‐domain (K2P) K+ channels. Altogether, the H2O2 induced increase in barium‐sensitive K+ conductance is likely an immediate response to increased ROS and mediates decreased neuronal activity.Grant Funding Source: Supported by: RO1 HL098602, AHA 12POST11670002 (TDO).