TY  - CPAPER
AU  - Barioni, N
AU  - Derakhshan, F
AU  - Lopes, L
AU  - Heidari, N
AU  - Bharadia, M
AU  - Roy, A
AU  - Baghdadwala, M
AU  - McDonald, F
AU  - Scheibli, E
AU  - Harris, M
AU  - Dutschmann, M
AU  - Onimaru, H
AU  - Okada, Y
AU  - Wilson, R
Y2  - 2020/12/15
Y1  - 2020/04/01
SN  - 0892-6638
UR  - http://hdl.handle.net/11343/254317
AB  - Objective: To study the cellular oxygen sensing mechanism and contribution of the SOS in responses to cardiorespiratory crisis.         

Methods: We investigated the cellular mechanism of oxygen sensing in artificially‐perfused (in situ) and slice (in vitro) thoracic spinal cord preparations, recording sympathetic nerve root and single cell responses to hypoxia during pharmacological interrogation. To determine if the SOS are involved in cardiorespiratory responses to asphyxia, we also used an in situ rat spinal cord – carotid body ‐ brainstem preparation in which each oxygen sensitive compartment is separately perfused while recording phrenic (respiratory) and splanchnic (sympathetic) nerve activity.         

Results: Our data suggest the SOS use a novel oxygen sensing mechanism. This mechanism involves two interacting NADPH and oxygen‐dependent enzymes: Neuronal Nitric Oxide Synthase (NOS1) and NADPH oxidase (NOX2). NOS1 is expressed in surprising abundance in the SOS and is oxygen sensitive across the entire physiological range. Hence, in the presence of oxygen, NOS1 is likely to utilize most of the available NADPH in the cell. When oxygenation falls during hypoxia, NOS1 activity is reduced, increasing NADPH availability for NOX2. NOX2 produces Reactive Oxygen Species (ROS) which in turn, activate ROS‐dependent internal Ca2+ stores and/or Ca2+ channels leading to increased intracellular Ca2+, neuronal firing and, consequently, SOS responses to hypoxia. Functionally, during hypoxia, the SOS enhance sympathetic and breathing activity, while shortening apnea and gasping towards recovery, and are capable of triggering brief periods of sympathetic and respiratory‐like activity in the brainstem’s absence.         

Conclusions: The results provide critical new knowledge required to unlock the cellular mechanisms involved in how the body mounts emergency responses to conditions that involve chronic and acute hypoxia.
LA  - English
PB  - WILEY
T1  - Spinal Oxygen Sensors (SOS): A Novel Oxygen Sensing Mechanism Involved in Cardiovascular Responses to Hypoxia
DO  - 10.1096/fasebj.2020.34.s1.03781
IS  - The FASEB Journal
VL  - 34
IS  - S1
ER  -