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

The nTS holds a vital role in cardiorespiratory reflexes as the first central integration site of chemosensitive afferents. Hypoxia‐reoxygenation over‐produces H 2 O 2 , 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 H 2 O 2 . This was due to a reversible hyperpolarization in resting membrane potential (RMP; ‐10 mV) and reduction in membrane resistance ( R i ; ‐224 MΩ). Since these effects occur at RMP (~ ‐60 mV), we determined the effect of H 2 O 2 on K + channel conductance using voltage steps and ramps between ‐100 and ‐50 mV in nTS slices. H 2 O 2 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 H 2 O 2 was also observed during voltage ramps. Conductance changes persisted during blockade of glutamate and GABA A receptors, confirming such effects were not secondary to synaptic activation. H 2 O 2 ‐induced alterations of RMP, R i and slope conductance were eliminated by barium (100 µM), a blocker of inward rectifying (IRK) and 2‐pore‐domain (K 2P ) K + channels. Altogether, the H 2 O 2 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).