[Intracellular calcium homeostasis in sensory neurons during hypoxia]. / Vnutrishn'oklitynnyi kal'tsiievyi homeostaz sensornykh neironiv pry hipoksychnykh vplyvakh.

Hypoxia is the main reason leading to neuronal death during different forms of brain diseases. The main phenomenon observed at hypoxia is excessive growth of intraneuronal Ca2+ concentration leading to irreversible cell damage. Despite extensive studies of this process, the intracellular mechanisms responsible for disturbance in Ca2+ are still unclear. The aim of present investigations was to explore these mechanisms. Ca2+ was measured by spatial screening of isolated dorsal root ganglion (sensory) neurons loaded with fluorescent dye Fura-2AM after exposing them hypoxic solution. Hypoxia resulted in a reversible elevation of Ca2+, which could be partly prevented by several pharmacological agents. We concluded that in sensory neurons hypoxia-induced elevation of cytosolic Ca2+ is induced by primary changes in ionic channels and secondary in function of mitochondria.

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

Elevation of cytosolic level of Ca(2+) was measured by spatial screening of freshly isolated dorsal root ganglion neurons loaded with Fura-2AM after subjecting them to a moderate hypoxic solution (pO(2)=10-40 mmHg). Short exposure of neurons to hypoxia resulted in a reversible elevation of intracellular Ca(2+) to about 120% in the cell center and to 80% in the cell periphery. Such elevation could be almost completely eliminated by removal of Ca(2+) 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 Ca(2+) is induced by combined changes of function in three cell substructures: voltage-operated L-type Ca(2+) and Na(+) channels and Ca(2+) accumulation by mitochondria. Mitochondria are important for spatial difference in the hypoxia-induced Ca(2+) elevation due to their specific location in these neurons.