Calcium-induced degeneration of axoplasm in isolated segments of rat peripheral nerve

Abstract

Comparative studies were conducted on the pattern of degenerative changes in transected rat saphenous nerves and in excised segments of the same nerve incubated at 37°C in dextrose-enriched oxygenated Ringer's solution with varying calcium ion concentrations. Identical features of Wallerian degeneration were observed in the transected nerve and in nerve segments incubated in Ringer's solution. A characteristic initial alteration of this process was the granular disintegration of axoplasmic microtubules and neurofilaments, a phenomenon which was shown to be calcium-dependent in the isolated nerve segments. This primary axonal alteration as well as the associated linear fragmentation of myelin sheaths could be prevented by substitution of equimolar concentrations of magnesium for calcium (Ca-free media) or by the addition of 10 m M EGTA (Ca-chelated media) to Ringer's solution. Furthermore, the granular disintegrative axoplasmic change could be accelerated by the addition of 10 or 50 m M CaCl 2 to Ringer's incubation media or by subjecting the nerve preparations to chemical (detergent) or physical (freeze-thawing) membrane disrupting procedures. These findings support a Ca-influx hypothesis of Wallerian degeneration, whereby degradative axonal membrane alterations and a spontaneous influx of calcium ion into the axoplasm are critical phenomena in the degeneration of isolated axons.