Mitochondrial electron transport chain activity is not essential for the acute hypoxic response of spinal oxygen sensors.

Spinal sympathetic preganglionic neurons (SSPNs) are oxygen sensitive. These spinal oxygen sensors (SOS) increase sympathetic output when subjected to acute hypoxia, orchestrating cardiorespiratory responses to protect against the deleterious effects of oxygen deprivation. Most other oxygen-sensing systems rely on mitochondrial mechanisms to detect and signal decreases in oxygen. Here, we apply pharmacological blockers of the mitochondrial respiratory chain and a mitochondrial-targeted antioxidant to a rat perfused in situ spinal cord preparation to test the role of mitochondria in the SOS. We demonstrate that, unlike other oxygen-sensitive cells, the mitochondrial respiratory chain is not essential for the SOS. Nonetheless, blockade of mitochondrial respiratory complexes augments SSPN activity. These results indicate that mitochondrial reactive oxygen species (ROS) can increase SSPN activity but do not appear to drive the SOS. We propose that, in chronic diseases prone to oxidative stress and/or frequent hypoxic events, SSPN mitochondrial ROS directly contribute to sympathetic overactivity. KEY POINTS: Decreases in oxygen concentration are detected by oxygen-sensitive cells that orchestrate cardiorespiratory and vascular adjustments to avoid oxygen deprivation to vital tissues. Recently discovered spinal oxygen sensors (SOS) increase sympathetic and respiratory activity in response to hypoxia. Unlike other oxygen-sensitive cells, here we report that the SOS do not rely on the mitochondrial electron transport chain for oxygen sensing. Our findings show that pharmacological blockade of mitochondrial respiratory complexes can increase sympathetic activity but does not inhibit the hypoxic response. These results indicate that mitochondrial reactive oxygen species can affect sympathetic activity, but that mitochondria do not appear to play a key role in spinal oxygen sensing.