A functional role for the mitochondria in acute O2 sensing in the carotid body (CB) remains undetermined. Whilst total inhibition of mitochondrial activity causes intense CB stimulation, it is unclear whether this response can be moderated such that graded impairment of oxidative phosphorylation might be a mechanism that sets and modifies the O2 sensitivity of the whole organ. We assessed NADH autofluorescence and [Ca(2+)]i in freshly dissociated CB type I cells and sensory chemoafferent discharge frequency in an intact CB preparation, in the presence of varying concentrations of nitrite (NO2 (-)), a mitochondrial nitric oxide (NO) donor and a competitive inhibitor of mitochondrial complex IV. NO2 (-) increased CB type I cell NADH in a manner that was dose-dependent and rapidly reversible. Similar concentrations of NO2 (-) raised type I cell [Ca(2+)]i via L-type channels in a PO2-dependent manner and increased chemoafferent discharge frequency. Moderate inhibition of the CB mitochondria by NO2 (-) augmented chemoafferent discharge frequency during graded hypoxia, consistent with a heightened CB O2 sensitivity. Furthermore, NO2 (-) also exaggerated chemoafferent excitation during hypercapnia signifying an increase in CB CO2 sensitivity. These data show that NO2 (-) can moderate the hypoxia sensitivity of the CB and thus suggest that O2 sensitivity could be set and modified in this organ by interactions between NO and mitochondrial complex IV.
- carotid body
- Nitric oxide