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Journal of Neuroscience, Vol 11, 2582-2587, Copyright © 1991 by Society for Neuroscience
Sustained increase in intracellular calcium promotes neuronal survival
F Collins, MF Schmidt, PB Guthrie and SB Kater
Synergen, Incorporated, Boulder, Colorado 80301.
Ciliary ganglion neurons, half of which normally suffer developmental death
in the embryo, will survive in culture in medium supplemented with
depolarizing concentrations of potassium. It is not known how elevated
potassium acts inside the cell to promote survival. We report here that
depolarizing concentrations of extracellular potassium promote neuronal
survival by causing a sustained increase in intracellular calcium. Raising
extracellular potassium from 5 to 40 mM, an optimal concentration for
survival, caused a sustained increase in intracellular calcium from 250 nM
to greater than 600 nM. By 26 hr, at which time greater than 90% of neurons
in 5 mM potassium had died, the calcium concentration of neurons in 40 mM
potassium was still above 400 nM. Reduction of extracellular potassium from
40 to 5 nM, which prevents the increase in survival, also reduced
intracellular calcium back to rest levels. PN200-110, a dihydropyridine
calcium channel blocker that inhibits the survival-promoting effect of
elevated potassium, also prevented and reversed the potassium,-mediated
increase in intracellular calcium. In addition, there was a strong,
quantitative correlation between the percentage of neuronal survival and
the intracellular calcium concentration over a wide range of extracellular
potassium concentrations. These results suggest that elevated potassium
opens dihydropyridine-sensitive calcium channels, causing a sustained
increase in intracellular calcium that quantitatively determines the number
of surviving neurons.
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