Axotomy induces a transient and localized elevation of the free
intracellular calcium concentration to the milimolar range.
Ziv, Noam E., Micha E. Spira.
From.
APStracts 2:0197N, 1995.
SUMMARY AND CONCLUSIONS
1. Axonal transection triggers a cascade of pathological processes that
frequently lead to the degeneration of the injured neuron. It is generally
believed that the degenerative process is triggered by an overwhelming influx
of calcium through the cut end of the axon. 2. Theoretical considerations and
indirect observations suggest that axotomy is followed by an increase in the
free intracellular calcium concentration ([Ca 2+ ] i ) to the milimolar level.
In contrast, only relatively modest and transient elevation in [Ca 2+ ] i to
the micromolar level was revealed by recent fura-2 studies. 3. In the current
study we have used the low-affinity Ca 2+ indicator mag-fura-2 (furaptra) to
reexamine the spatiotemporal distribution pattern of Ca 2+ following axotomy
and to map the free intracellular Mg 2+ concentration gradients. 4. We report
that axotomy elevates [Ca 2+ ] i well beyond the "physiological" range of
calcium concentrations, to levels exceeding 1 milimolar near the tip of the
cut axon and to hundreds of micromolars along the axon further away from the
cut end. Nevertheless, [Ca 2+ ] i recovers to the control levels within 2-3
minutes following the resealing of the cut end. 5. A comparison of the
behavior of fura-2 and mag-fura-2 in the cytosol of the axotomized neurons
reveals that the determination of [Ca 2+ ] i by fura-2 largely underestimates
the actual intracellular Ca 2+ concentrations. 6. Experiments in which one
branch of a bifurcated axon was transected revealed that the elevation in [Ca
2+ ] i is confined to the transected axonal branch, and does not spread beyond
the bifurcation point. 7. Following axotomy, the intracellular Mg 2+
concentration equilibrates rapidly with the external concentration, and then
recovers at a rate somewhat slower than that of [Ca 2+ ] i . 8. To the best of
our knowledge, this study is the first direct demonstration that axotomy
elevates [Ca 2+ ] i to the milimolar range and that neurons are able to
recover from these extreme calcium concentrations.
Received 10 January 1995; accepted in final form 20 June 1995.
APS Manuscript Number J24-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.