Expression and Function of Oxytocin Signaling on Nodose Sensory Neuron Potassium Currents after Chronic Intermittent Hypoxia (CIH)
Authors: Dantzler Heather A. , Kline David D. 
Published: June 2021

Hypothalamic‐derived oxytocin (OT) increases systemically and in the dorsal vagal complex in response to a variety of stimuli and stressors, such as hypoxia. Within the nucleus tractus solitarii (nTS), OT modifies baroreflex sensitivity suggestive of an influence of OT on presynaptic afferents originating in the nodose ganglia or postsynaptic nTS neurons. nTS slice studies demonstrated an excitatory influence of OT on afferent terminals, and nodose neurons express the OT receptor (OTR) whose activation elevates somal calcium. The hypoxic stressor obstructive sleep apnea, and its CIH animal model, elevates blood pressure and alters heart rate variability. During CIH, however, enhancing OT in the dorsal vagal complex reduces blood pressure. To determine the mechanism(s) by which OT and OTR modulates sensory afferent‐nTS activity and mediated reflexes normally and after CIH we used immunohistochemistry, immunoblot, and electrophysiology on nodose ganglia tissue. Nodose ganglia of 5–6 week old male and female Sprague‐Dawley rats were studied after 10 days of Normoxia (Norm, 21% O2) or CIH (alternating 21% & 6% O2, 8 hr/day). Immunohistochemistry of cryostat‐sectioned (10 μm) nodose ganglia demonstrated OTRs in a subset of Norm somas and fibers. Immunoblot demonstrated a 0.52 fold reduction in OTR protein after CIH vs. Norm (n=4 each). OT plasma levels were reduced in CIH (n=12) when compared to Norm (n=10). To determine the functional effects of these changes, nodose neurons were dissociated, and 2–5 hours after isolation outward potassium currents (IK) were evoked via depolarizing voltages (10 mV steps, −70 to +60 mV, 140 ms) from a holding potential of −60 mV. The IK‐voltage relationship was measured in the presence of vehicle or 600 nM OT with or without the application of the OTR antagonist L‐368,899 (1 μM). OT‐sensitive IK was also characterized by the application of the K+ channel blockers Tetraethylammonium (TEA, 10 mM) or 4 ‐Aminopyridine (4‐AP, 5 mM), prior to and during the application of vehicle or 600 nM OT. In male nodose neurons, vehicle application after Norm and CIH did not alter IK, confirming no time dependent changes in IK. By contrast, OT decreased IK after Norm (n=7) and CIH (n=9), with the attenuation more prominent in CIH. The application of the OTR antagonist or TEA prior to and during 600 nM OT blocked the reduction of IK in CIH (n=5–7) and Norm (n=4–5). Conversely, 4‐AP did not block the OT‐reduction in IK after CIH (n=4) and Norm (n=6). To determine if there was a sex‐dependent influence of OT on IK, female nodose neurons were examined. OT induced a similar reduction of IK as males (n=5). Taken together, these data demonstrate OTR in nodose ganglia neurons and its activation via OT induces decreases IK that are consistent with increasing excitability in CIH. These data may also shed light on the influence of OT blood pressure control.

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RO1 HL128454 & HL098602

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.