INV47

Acute oxygen sensing in health and disease

J López-Barneo(1)

1: Institute of Biomedicine of Seville (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla

Oxygen (O₂) is needed for survival of most life forms on Earth and, therefore, the supply of sufficient O₂ to the tissues is a major physiological challenge. In mammals, a deficit of O₂ (hypoxia) triggers rapid cardiorespiratory reflexes (e.g. hyperventilation and increased heart output) that within a few seconds increase the uptake of O₂ by the lungs and its distribution throughout the body. These adaptive responses are essential for adaptation to high altitudes and for survival of patients with restrictions of gas exchange in the lungs. The prototypical organ within the “homeostatic acute O₂ sensing system” is the carotid body (CB), which contains sensory glomus cells expressing O₂-regulated ion channels. In response to hypoxia, glomus cells depolarize and release transmitters, which activate afferent fibers terminating at the brainstem respiratory and autonomic centers. The nature of the glomus cell O₂ sensor has been elusive but recent data have shown that these cells contain specialized mitochondria expressing high levels of specific enzymes and atypical electron transport chain (ETC) subunit isoforms. Glomus cells combine an accelerated ETC and high O₂ consumption with a cytochrome c oxidase having a low apparent affinity for O₂. Hypoxia causes a slowdown of the ETC resulting in the accumulation of NADH and the production of H₂O₂, which are the signals that regulate membrane ion channels. Alterations of CB output can contribute to the pathophysiology of highly prevalent diseases such as respiratory depression, sleep apnea, or refractory hypertension. Disruption of the CB O₂ sensor may be also the cause of silent hypoxemia characteristic of some COVID-19 patients.