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SUMMARY:Mitochondria and acute oxygen sensing by arterial chemoreceptors -
  Professor José López Barneo | Instituto de biomedicina de Sevilla 
DTSTART:20190529T140000Z
DTEND:20190529T150000Z
UID:TALK118630@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:Oxygen (O2) is essential for life\, particularly in mammals\, 
 due to its role as an electron acceptor in oxidative phosphorylation. An O
 2 deficit (hypoxia)\, even if transient\, can produce severe pathological 
 consequences in sensitive tissues such as the brain or heart. Changes in O
 2 tension (PO2) alter the activity of O2-sensitive ion channels in tissues
  of the homeostatic acute O2-sensing system\, thereby leading to compensat
 ory responses. The best-studied arterial chemoreceptors are the carotid bo
 dy (CB) glomus cells\, which contain O2-sensitive K+ channels in the plasm
 a membrane. Inhibition of these channels during hypoxia leads to cell depo
 larization\, Ca2+ influx through voltage-gated channels\, and exocytotic t
 ransmitter release\, which activates sensory fibers terminating in the bra
 instem. This chain of events induces hyperventilation and sympathetic acti
 vation in a time scale of seconds. Although this membrane model of acute O
 2 sensing is widely accepted\, the mechanisms underlying detection of O2 l
 evels by ion channels have remained elusive. The responsiveness of glomus 
 cells to hypoxia is prevented by rotenone\, a blocker of mitochondrial com
 plex I (MCI)\, which competes with the binding of ubiquinone. Genetically-
 modified mice lacking the Ndufs2 gene\, which encodes an MCI protein essen
 tial for ubiquinone binding\, show a lack of ventilatory response to hypox
 ia and a loss of sensitivity of glomus cells to decreases in PO2. Gene exp
 ression profile analyses have shown that O2-sensing glomus cells in the CB
  express specific ion channels\, metabolic enzymes and mitochondrial subun
 its. Cellular experiments suggest that hypoxia induces a slow-down of the 
 electron transport chain in these cells\, resulting in an increased QH2/Q 
 ratio. This\, in turns\, induces NADH accumulation and the production of r
 eactive oxygen species that inhibit the activity of K+ channels. These dat
 a suggest a mitochondria-to-membrane signaling mechanism\, which provides 
 a comprehensive model that explains acute O2 sensing.   
LOCATION:Sackler Lecture Theatre (Level 7) The Keith Peters Building\, Cam
 bridge Biomedical Campus
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