Intracellular mechanisms of hypoxia-induced calcium increase in rat sensory neurons

Elevation of cytosolic level of Ca2+ was measured by spatial screening of freshly isolated dorsal root ganglion neurons loaded with Fura-2AM after subjecting them to a moderate hypoxic solution (pO2=10–40 mm Hg). Short exposure of neurons to hypoxia resulted in a reversible elevation of intracellular Ca2+ to about 120% in the cell center and to 80% in the cell periphery. Such elevation could be almost completely eliminated by removal of Ca2+ or Na+ from external medium or application of nifedipine, an L-type calcium channel blocker. Remarkable antihypoxic efficiency (58%) was achieved by preapplication of mitochondrial protonophore CCCP. A conclusion is made that in sensory neurons the hypoxia-induced elevation of cytosolic Ca2+ is induced by combined changes of function in three cell substructures: voltage-operated L-type Ca2+ and Na+ channels and Ca2+ accumulation by mitochondria. Mitochondria are important for spatial difference in the hypoxia-induced Ca2+ elevation due to their specific location in these neurons.