Oxytocin Reduction of Nodose Ganglion Neurons Potassium Currents is Enhanced in Chronic Intermittent Hypoxia (CIH)

Oxytocin (OT) from the hypothalamus is increased in several cardiorespiratory nuclei and the circulation in response to a variety of stimuli and stressors, including hypoxia. Oxytocin within the nucleus tractus solitarii (nTS) enhances synaptic transmission, action potential (AP) discharge, and cardiac baroreflex gain to lower heart rate. The baroreceptor reflex is mediated through afferent neurons whose somas originate in the nodose ganglia and project centrally to the nTS. Nodose neurons express the OT receptor, and its activation elevates intracellular calcium; the influence of OT on other ion channels, especially during hypoxia, is not known. The hypoxic stressor obstructive sleep apnea, and its CIH animal model, elevates blood pressure and alters heart rate variability. Recent studies suggest enhancing OT in the dorsal vagal complex during CIH may reduce blood pressure. This study was undertaken to determine the mechanism(s) by which OT modulates sensory afferent‐nTS mediated reflexes normally and after CIH. Nodose neurons of 5–6 wk old male Sprague‐Dawley rats were isolated after 10 d of Normoxia (21% O 2 , Norm) or CIH (alternating 21% & 6% O 2 , 8 hr/day). Two‐5 hrs after isolation, we recorded outward potassium currents (I K ) and APs by the patch clamp method. To examine I K , neurons were held at −60 mV and currents were evoked by depolarizing voltages (−70 to +60 mV, 140 ms). The steady state I K ‐voltage relationship was analyzed. AP discharge was evoked by injecting 50 pA depolarizing steps (−20 to 280 pA, 200 ms); the current‐discharge relationship was evaluated. I K and APs were examined during baseline and after 3 min of vehicle or OT (300, 600, or 1000 nM). Vehicle did not alter I K in Norm (n=6) and CIH (n=4) cells, confirming lack of time‐dependent I K changes. In Norm cells, OT decreased I K at voltages greater than +40 mV (300 nM, n=8) and +60 mV (600 nM, n=7). After CIH, OT (300 nM, n=5) also decreased I K at +40 mV and greater. OT at 600 nM (n=5) attenuated I K at significantly lower voltages (+20 mV) in CIH vs. Norm. OT‐sensitive currents at +60 mV were greater in CIH than Norm at 300 and 600 nM. In Norm and CIH groups (n=4, 5), OT at 1000 nM had variable I K responses which overall were not significantly different from baseline. Fitting I K s to Boltzmann functions demonstrated a reduction in half‐activation during OT in Norm cells. In Norm and CIH cells, application of the K + channel blocker tetraethylammonium (TEA, 10 mM) decreased I K and blocked the OT‐induced reduction in I K (600 nM, n=3). Depolarizing nodose neurons with up to 280 pA injection induced APs in Norm (n=7) and CIH (n=5) neurons, and 600 nM OT did not alter the number of APs during a given current step. Yet, 600 nM OT decreased AP threshold and tended to increase AP half‐width in CIH but not Norm cells, consistent with the reduction in I K by OT in CIH. In Norm cells, vehicle and OT did not alter holding currents measured at −60 mV, but after CIH 600 nM OT induced modest depolarizing inward currents. Taken together, these data demonstrate OT induces changes in ionic currents in nodose ganglia cells that are consistent with increasing excitability in CIH, and may also shed light on the bradycardic and anti‐hypertensive action of OT. Support or Funding Information RO1 HL 128454 & HL 098602 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .