The long-range goal is to identify the cellular and molecular mechanisms of O2 chemoreception specifically in the carotid body (CB) which may be applicable to other known O2 sensing systems. The consensus model is that the glomus cell in the CB is the chemoreceptor which upon stimulation mobilizes Ca2+, activates neurotransmitter release and the sensory discharge.
The specific aims are designed to test the hypothesis that PO2-dependent mitochondrial energy metabolism is the primary sensor. We plan to use CO to reversibly block cytochrome a2+3 in the perfused- superfused CB and in the separated glomus cell. On the other hand, by binding with the putative membrane home CO would block the A+ conductance decrease due to hypoxia. Thus CO would have opposite effects with respect to cytochrome a2+3 and the membrane heme -- the former being excitatory and the latter inhibitory. There is no other explanation for the excitatory response by CO than by it, intracellular complex formation unless acid is formed. This acid formation could explain a part of the CO effect. Using the sensory discharges we plan to measure the following effects of CO on CB: titrate the O2 up take and sensory activity with and without light; response to CO2 -H+ with and without light, on the blockade of energy-state and membrane sulphydryls; response to different wavelengths of light; pHi response; dependence on extracellular [Ca2+] and on vascular PO2 distribution. We also plan to measure the effects of Co on pHi and [Ca2+]1 of separated glomus cells. The experimental measurements are: chemosensory discharge, CB PO2 by the phosphorescence imaging and microelectrode techniques and intracellular pH by the fluorescence imaging and intracellular [Ca2+] and pH of dissociated and cultured glomus cell by spectrofluorimetry. Broad significance of the study concerns principle of O2 chemoreception, and its lobs and disorder and its alleviation. The second level of significance involves reflex functions (e.g., control of ventilation, airway and vascular smooth muscles, sleep apneas, etc.). Carotid bodies provide the major gateway for the organism to receive signals due to low PO2 in the lung and blood, and to generate life-saving reflex responses against hypoxia and asphyxia.
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