Effect of Superior Cervical Gangionectomy on the Chemoreflex Response to Hypoxia in the Rat Carotid Body

Abstract

Carotid body (CB) chemosensitive glomus (type I) cells respond to decreases in blood pO2 (hypoxia) by releasing neurotransmitters, which in turn activate adjacent chemosensory afferent fibers within the carotid sinus nerve (CSN). These CSN chemoafferents then signal to the commissural nucleus tractus solitarius (cNTS) within the dorsal brainstem, which leads to a compensatory increase in ventilation in order to restore blood‐gas homeostasis. The CB receives sympathetic innervation via the ganglioglomerular nerve (GGN), whose cell bodies reside in the superior cervical ganglion (SCG). We have found that electrical stimulation of the GGN causes an increase in CB chemosensory afferent discharge. However, it is unknown the effect removing the carotid body’s sympathetic innervation, via superior cervical ganglionectomy, will have on the carotid body’s chemoreflex response to hypoxia. We hypothesize that loss of sympathetic input will decrease the hypoxic ventilatory response (HVR) of the rat, and alter the O2‐sensing mechanism of the CB chemosensitive glomus cells. Sprague Dawley male rats postnatal day 21 were subjected to unilateral or bilateral superior cervical ganglionectomy (SCGX). Four days post surgery (post‐natal day 25), rats either underwent whole body plethysmography recordings or were sacrificed and their carotid bodies removed to either isolate glomus cells and perform whole cell perforated patch clamp, or perform immunohistochemistry on the CB. Our preliminary results show that unilateral (left or right) SCGX appears to decrease the HVR during a 1‐minute exposure to hypoxia (10% O2, 90% N2) compared to bilateral SCGX. Our results also show that following SCGX, isolated glomus cells responded to acute hypoxia (HX) (5–8% O2, 5% CO2, balanced N2) with significant reductions (P<0.05 to P<0.01) in outward K+ current amplitudes over the test potential range +10 to +60 mV. The mean maximal effect, a reduction in K+ amplitude of 64.9 ± 18.5% (mean ± SD, n = 3 cells), occurred at a Vtest of +30mV. In contrast, control carotid body glomus cells responded to acute HX with a significant reduction (P<0.05) in outward K+ current amplitude at a Vtest of +60mV (n = 4 cells). In conclusion, our data suggests that sympathetic innervation to the CB is critical for the ventilatory response to hypoxia, and the O2‐sensing mechanism at the level of the CB glomus cells. Overall this study provides novel evidence for the importance of sympathetic innervation on peripheral chemosensors during exposure to hypoxia.Support or Funding InformationThis work was supported in part by a SPARC NIH award OT2OD023860