Research PaperSealing frequency of B104 cells declines exponentially with decreasing transection distance from the axon hillock

- Axon sealing exponentially declines with decreasing transection distance from hillock.
- Time course of axonal sealing depends on transection distance from axon hillock.
- Axon sealing frequency and time course could affect calcium influx and cell survival.

Transection of nerve axons (axotomy) leads to rapid (Wallerian) degeneration of the distal portion of the severed axon whereas the proximal portion and the soma often survive. Clinicians and neuroscientists have known for decades that somal survival is less likely for cells transected nearer to the soma, compared to further from the soma. Calcium ion (Ca2 +) influx at the cut axonal end increases somal Ca2 + concentration, which subsequently activates apoptosis and other pathways that lead to cell death. The same Ca2 + influx activates parallel pathways that seal the plasmalemma, reduce Ca2 + influx, and thereby enable the soma to survive. In this study, we have examined the ability of transected B104 axons to seal, as measured by uptake or exclusion of fluorescent dye, and quantified the relationship between sealing frequency and transection distance from the axon hillock. We report that sealing frequency is maximal at about 150 μm (μm) from the axon hillock and decreases exponentially with decreasing transection distance with a space constant of about 40 μm. We also report that after Ca2 + influx is initiated, the curve of sealing frequency versus time is well-fit by a one-phase, rising exponential model having a time constant of several milliseconds that is longer nearer to, versus further from, the axon hillock. These results could account for the increased frequency of cell death for axotomies nearer to, versus farther from, the soma of many types of neurons.

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