Mitochondrial function and carotid body transduction.
Carotid body chemoreceptors respond to a decrease in arterial oxygen tension by increasing spiking activity on the sinus nerve. Our understanding of the oxygen-transducing ability of the organ arose from studies in the 1930s intended to understand how metabolic poisons stimulated breathing. Since that time, an intimate link between energy state and hypoxia sensing has been assumed and forms the basis of the metabolic hypothesis of oxygen sensing. This hypothesis is supported by studies demonstrating a loss of mitochondrial potential in carotid body cells at oxygen tensions that cause no change in cells from other tissues. Although the nature of the coupling between mitochondrial function and nerve excitation remains unresolved, experimental evidence supports roles for (1) release of mitochondrial calcium stores, (2) modulation of membrane channels that are linked to mitochondrial complexes I and IV, and (3) generation of signaling intermediates, such as reactive oxygen species (ROS) from complex I and III of the electron transport chain. If the mitochondrion is the oxygen-sensing site for peripheral chemoreceptors, then there exists the potential ability to manipulate, perhaps pharmacologically, the sensing function by alterations in expression of uncoupler proteins or chemicals that can alter the affinity of cytochrome oxidase for oxygen. Such manipulation may be useful for the treatment of hypoventilation syndromes or high altitude accommodation.
Donnelly
David F
DF
Department of Pediatrics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. David.Donnelly@Yale.edu
Carroll
John L
JL
D000064:Acclimatization; D002344:Carotid Body / Q000098:blood supply* / Q000378:metabolism*; D002908:Chronic Disease; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009051:Mountaineering; D018384:Oxidative Stress; D010101:Oxygen Consumption / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species