and Specific Aims.) The broad objectives of this application are to gain deeper insight into the mechanisms operating during the carotid body's (cb) chemotransduction of hypoxia, hypercapnia, and acidosis into increased neural activity recordable in the carotid sinus nerve. On the assumption that (a) the essential chemotransductive unit consists of the Type I cell and the apposed neuron, (b) that hypoxia depolarizes the Type I cell provoking the release of neuroagent(s) which bind to a receptor(s) on the apposed neuron, and (c) this initiates processes responsible for the recordable action potentials in the carotid sinus nerve, two questions can be asked: (1) How is the Type I cell depolarized so as to release the neuroagents? (2) What are the essential excitatory and inhibitory neuroagents in the cat and how are they managed? This application addresses the second question.Five areas of research are proposed, each containing focused hypotheses to be tested: (1) Analyze the venous effluent from the in situ cat carotid body for neurotransmitters (Are those released during hypercapnia the same as those released during hypoxia?); (2) Identify the cb's excitatory and inhibitory neurotransmitters and their pharmacological interaction (Does the cb respond more to hypoxia in the presence of an M2 receptor blocker?); (3) Determine the presence and location of specific neurotransmitter receptors (Is there a neuronal nicotinic receptor on the dendrite apposed Type I cell?); (4) determine the effect of cholinergic agonists and dopamine on membrane potential and potassium channels of the Type I cells (What does ACh do to the calcium-activated potassium current?); (5) Repeat the studies of (2) in the rabbit which responds differently from the cat. Techniques include neural recording, HPLC analysis, immunocytochemistry, and patch clamping cultured Type I cells. Better knowledge of how the cb works could perhaps allow the creation of an agent to temporarily block input from the cb.
| Fitzgerald, Robert S; Dehghani, Gholam A; Kiihl, Samara (2015) Organismal Responses to Hypoxemic Challenges. Adv Exp Med Biol 860:101-13 |
| Fitzgerald, Robert; DeSantiago, Breann; Lee, Danielle Y et al. (2014) H2S relaxes isolated human airway smooth muscle cells via the sarcolemmal K(ATP) channel. Biochem Biophys Res Commun 446:393-8 |
| Fitzgerald, Robert S; Dehghani, Gholam Abbas; Kiihl, Samara (2013) Autonomic control of the cardiovascular system in the cat during hypoxemia. Auton Neurosci 174:21-30 |
| Fitzgerald, Robert S; Dehghani, Gholam Abbas; Kiihl, Samara (2013) Autonomic regulation of organ vascular resistances during hypoxemia in the cat. Auton Neurosci 177:181-93 |
| Fitzgerald, Robert S; Shirahata, Machiko; Chang, Irene et al. (2012) Hydrogen sulfide acting at the carotid body and elsewhere in the organism. Adv Exp Med Biol 758:241-7 |
| Fitzgerald, Robert S; Cherniack, Neil S (2012) Historical perspectives on the control of breathing. Compr Physiol 2:915-32 |
| Fitzgerald, Robert S; Shirahata, Machiko; Chang, Irene et al. (2011) The impact of hydrogen sulfide (H?S) on neurotransmitter release from the cat carotid body. Respir Physiol Neurobiol 176:80-9 |
| Fitzgerald, Robert S; Shirahata, Machiko; Chang, Irene et al. (2009) The impact of hypoxia and low glucose on the release of acetylcholine and ATP from the incubated cat carotid body. Brain Res 1270:39-44 |
| Fitzgerald, Robert S; Shirahata, Machiko; Chang, Irene (2009) The impact of adenosine and an A2A adenosine receptor agonist on the ACh-induced increase in intracellular calcium of the glomus cells of the cat carotid body. Brain Res 1301:20-33 |
| Balbir, Alexander; Lande, Boris; Fitzgerald, Robert S et al. (2008) Behavioral and respiratory characteristics during sleep in neonatal DBA/2J and A/J mice. Brain Res 1241:84-91 |
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