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.
Lukyanetz
E A
EA
Bogomoletz Institute of Physiology, 01024 Kiev, Ukraine. elena@serv.biph.kiev.ua
Stanika
R I
RI
Koval
L M
LM
Kostyuk
P G
PG
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002462:Cell Membrane / Q000648:ultrastructure; D003600:Cytosol / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D000860:Hypoxia; D007476:Ionophores / Q000494:pharmacology; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D005456:Fluorescent Dyes; D007476:Ionophores; D002104:Cadmium; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D012964:Sodium; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2