A revisit to O2 sensing and transduction in the carotid body chemoreceptors in the context of reactive oxygen species biology.
Oxygen-sensing and transduction in purposeful responses in cells and organisms is of great physiological and medical interest. All animals, including humans, encounter in their lifespan many situations in which oxygen availability might be insufficient, whether acutely or chronically, physiologically or pathologically. Therefore to trace at the molecular level the sequence of events or steps connecting the oxygen deficit with the cell responses is of interest in itself as an achievement of science. In addition, it is also of great medical interest as such knowledge might facilitate the therapeutical approach to patients and to design strategies to minimize hypoxic damage. In our article we define the concepts of sensors and transducers, the steps of the hypoxic transduction cascade in the carotid body chemoreceptor cells and also discuss current models of oxygen- sensing (bioenergetic, biosynthetic and conformational) with their supportive and unsupportive data from updated literature. We envision oxygen-sensing in carotid body chemoreceptor cells as a process initiated at the level of plasma membrane and performed by a hemoprotein, which might be NOX4 or a hemoprotein not yet chemically identified. Upon oxygen-desaturation, the sensor would experience conformational changes allosterically transmitted to oxygen regulated K+ channels, the initial effectors in the transduction cascade. A decrease in their opening probability would produce cell depolarization, activation of voltage dependent calcium channels and release of neurotransmitters. Neurotransmitters would activate the nerve endings of the carotid body sensory nerve to convey the information of the hypoxic situation to the central nervous system that would command ventilation to fight hypoxia.
Gonzalez
C
C
Departamento de Bioquímica y Biología Molecular y Fisiología, Instituto de Biología y Genética Molecular y CIBER de Enfermedades Respiratorias, Universidad de Valladolid, Consejo Superior de Investigaciones Científicas e Instituto Carlos III, Facultad de Medicina, 47005 Valladolid, Spain. constanc@ibgm.uva.es
Agapito
M T
MT
Rocher
A
A
Gomez-Niño
A
A
Rigual
R
R
Castañeda
J
J
Conde
S V
SV
Obeso
A
A
D000818:Animals; D002344:Carotid Body / Q000166:cytology*; D002628:Chemoreceptor Cells / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D010100:Oxygen