Date of Award
Doctor of Philosophy (PhD)
Colin A. Nurse
Aortic bodies (ABs) are putative peripheral arterial chemoreceptors located near the aortic arch. They are hypothesized to contribute to O2 homeostasis by sensing arterial O2 content and initiating cardiovascular reflexes during hypoxia; however, information on their cellular physiology is lacking. The primary goal of this thesis was to elucidate chemosensory mechanisms among mammalian (rat) AB cells, located specifically at the bifurcation of the left vagus nerve and recurrent laryngeal nerve (RLN), where they are found in association with a group of local neurons (>30). In vagus nerve-RLN whole-mounts, AB chemoreceptor (type I) cells were immunoreactive against the vesicular acetylcholine (ACh) transporter, and were surrounded by nerve terminals immunopositive for purinergic P2X2 and P2X3 receptor subunits, suggesting that ACh and ATP may act as neurotransmitters as in the related carotid body. In a novel dissociated AB culture model, subsets of type I cells exhibited elevated intracellular Ca2+ responses to hypoxia, isohydric hypercapnia, isocapnic acidosis, and acidic hypercapnia, demonstrating their direct chemosensitivity for the first time. Interestingly, surviving local neurons also responded to these chemostimuli, suggesting that they are sensory. Patch clamp electrophysiological and Ca2+ imaging studies revealed functional heteromeric P2X2/3 and nicotinic ACh receptors on local neurons, consistent with ACh and/or ATP mediating chemotransmission between receptor cells and local neurons. These neurons were also found to be interconnected by electrical synapses. Finally, the short-term survival of red blood cells (RBCs) in AB cultures, along with the finding that blood-borne factors (e.g. ATP released from RBCs) may have access to AB nerve terminals in situ, implicates RBCs as O2-sensors in AB function. Altogether, these results suggest an important role for purinergic P2X2/3 receptors on local neurons/nerve terminals and ATP release from type I cells and RBCs, in the unique ability of ABs to sense and process information about blood O2 content.
Piskuric, Nikol A., "Anatomical Characterization and Cellular Physiology of Rat Aortic Body Chemoreceptors" (2012). Open Access Dissertations and Theses. Paper 7359.
McMaster University Library
Available for download on Monday, September 09, 2013