Recently, we have demonstrated that sensory neurons of rat lumbar dorsal root 
ganglia (DRG) respond to hypoxia with an activation of endothelial nitric oxide 
(NO) synthase (eNOS) resulting in enhanced NO production associated with 
mitochondria which contributes to resistance against hypoxia. Extracellular 
calcium is essential to this effect. In the present study on rat DRG slices, we 
set out to determine what types of calcium channels operate under hypoxia, and 
which upstream events contribute to their activation, thereby focusing upon 
mitochondrial complex II. Both the metallic ions Cd2+ and Ni2+, known to inhibit 
voltage-gated calcium channels and T-type channels, respectively, and verapamil 
and nifedipine, typical blocker of L-type calcium channels completely prevented 
the hypoxic neuronal NO generation. Inhibition of complex II by 
thenoyltrifluoroacetone at the ubiquinon binding site or by 3-nitropropionic 
acid at the substrate binding site largely diminished hypoxic-induced NO 
production while having an opposite effect under normoxia. An additional 
blockade of voltage-gated calcium channels entirely abolished the hypoxic 
response. The complex II inhibitor malonate inhibited both normoxic and hypoxic 
NO generation. These data show that complex II activity is required for 
increased hypoxic NO production. Since succinate dehydrogenase activity of 
complex II decreased at hypoxia, as measured by histochemistry and densitometry, 
we propose a hypoxia-induced functional switch of complex II from succinate 
dehydrogenase to fumarate reductase, which subsequently leads to activation of 
voltage-gated calcium channels resulting in increased NO production by eNOS.