Potential roles of ATP and local neurons in the monitoring of blood O₂ content by rat aortic bodies

Abstract

Aortic bodies are arterial chemoreceptors presumed to monitor blood O2 content by unknown mechanisms, in contrast to their well-studied carotid body counterparts, which monitor PO2 and /pH. We recently showed that rat aortic body chemoreceptors (type I cells), located at the left vagus-recurrent laryngeal nerve bifurcation, responded to PO2 and PCO2 /pH in a manner similar to carotid body type I cells. These aortic bodies are uniquely associated with a group of local neurons, which are also sensitive to these stimuli. Here, we hypothesized that these local neurons may contribute to monitoring blood O2 content. During perforated patch recordings, ATP, known to be released from (carotid body) type I cells and red blood cells during hypoxia, induced inward currents and excited ≈ 45% of local neurons (EC50 ≈ 1 μm), mainly via heteromeric P2X2/3 purinoceptors. While ATP also induced a rise in intracellular [Ca(2+)] in a subpopulation of these neurons, almost all of them responded to nicotinic cholinergic agonists. During paired recordings, several juxtaposed neurons showed strong bidirectional electrical coupling, suggesting a local co-ordination of electrical activity. Perfusion with Evans Blue dye resulted in labelling of aortic body paraganglia, suggesting they have ready access to circulatory factors, e.g. ATP released from red blood cells during hypoxia. When combined with confocal immunofluorescence, the dye-labelled regions coincided with areas containing tyrosine hydroxylase-positive type I cell clusters and P2X2-positive nerve endings. We propose a working model whereby local neurons, red blood cells, ATP signalling and low blood flow contribute to the unique ability of the aortic body to monitor blood O2 content.

Metabolic Influences Modulating Erythrocyte Deformability and Eryptosis

“…Purinergic signaling is involved in the response to low blood O 2 which triggers ATP release by erythrocytes, leading to the stimulation of P2 × 2/3 receptors in the aortic body [56]. The breakdown of ATP into ADP inhibits ATP release via a negative feedback, which involves the P2Y13 receptors in human erythrocytes [57].…”

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases

“…At variance with carotid bodies, which are clumped at a single site and are sensitive to arterial oxygen partial pressure, aortic bodies are patches of chemosensory cells innervated by the vagus nerve, distributed along the aortic arch. Their function is less explored in humans; in experimental animals they are sensitive to hemoglobin oxygen saturation ( Piskuric et al, 2014 ). Red blood cells release ATP via pannexin-I channels in response to the conformational change in desaturated hemoglobin, and ATP, in turn, activates P2X receptors on aortic bodies’ nerve terminals to enhance the response of local chemosensory cells, which are supposed to share the same transduction mechanism as carotid bodies ( Piskuric and Nurse, 2013 ).…”

Aortic Body Chemoreceptors Regulate Coronary Blood Flow in Conscious Control and Hypertensive Sheep

“…There is some evidence in the literature that the ABs may have a specialized role in monitoring blood flow to the heart and thereby regulating heart function. 16,17 In this context, stimulation of ABs has been shown to increase peripheral vascular resistance 10,18 and produce either bradycardia or tachycardia. 8,9,12,19,20 The heart rate response to chemoreceptor stimulation is known to be species, respiratory, and arousal state-dependent.…”