Date of Award
Doctor of Philosophy (PhD)
Professor Colin A. Nurse
Paraganglion neurons within the rat glossopharyngeal nerve (GPN) are part of a nitric oxide synthase (nNOS)-synthesizing plexus of nerve fibers that innervate a chemosensory organ, the carotid body (CB). This thesis focused on the anatomical, biophysical, pharmacological, and immunocytochemical characterization of these GPN neurons with a view towards understanding their role in efferent CB inhibition. GPN neurons were grouped in two distinct populations, a proximal one near the bifurcation with the carotid sinus nerve, and a more distal one concentrated further along the GPN. Both neuronal populations shared similar passive membrane properties and expressed voltage-dependent Na+, K+, and a broad spectrum ofCa2+ channels which included L-, N, P/Q-, R- and T- types. In addition, they expressed a novel 02-sensitive K+ conductance, mediated via voltage-independent background or 'leak' K+ channels. Hypoxia depolarized and/or increased excitability in GPN neurons via inhibition of these 'leak' K+ channels, whose pharmacology suggested involvement of the tandem pore domain, halothane inhibited K+ (THIK) channel family. Indeed, when THIK-l channels were heterologously expressed in HEK 293 cells, the resulting K+ currents were found to be reversibly inhibited by hypoxia. GPN neurons were also sensitive to several neurotransmitters including acetylcholine, dopamine, serotonin and importantly, ATP, acting via multiple ionotropic P2X receptors. Pharmacological and confocal immunofluorescence studies suggested that these P2X receptors consisted of at least heteromeric P2X2-P2X3, homomeric P2X4 and homomeric P2X7 receptors. In cocultures of GPN neurons and CB chemoreceptor (type I) cell clusters, activation of P2X receptors on adjacent GPN neurons caused NO-dependent hyperpolarization of type I cells. Taken together these findings suggest key roles for hypoxia and ATP in the activation of GPN neurons, leading to Ca2 + entry, NOS activation, and NO-mediated inhibition of carotid body function.
Campanucci, Veronica A., "ELECTROPHYSIOLOGICAL PROPERTIES, POz- AND ATP-SENSITIVITY OF PARAGANGLION NEURONS OF THE RAT GLOSSOPHARYNGEAL NERVE" (2004). Open Access Dissertations and Theses. Paper 1611.