Structural alterations of peripheral nerve induced by the calcium ionophore A23187

Desheathed segments of rat peripheral nerve were incubated at 37 degrees C in oxygenated Ringer's solution with and without the addition of calcium ionophore, A23187, 10 microgram/ml. Nerve fibers incubated in the presence of both ionophore and calcium revealed extensive granular disintegration of their axonal microtubules and neurofilaments after 30 and 60 min incubation intervals. These changes were not seen following control incubations in Ringer's solution without ionophore or in calcium-free Ringer's solution containing ionophore and EGTA, 1 mmole/1. Ionophore-induced alterations were also noted in Schwann cell cytoplasm. The granular degradative alteration of axoplasm caused by exposure of nerve fibers to ionophore and calcium were believed to be due to an ionophore-mediated influx of calcium into the axoplasm with resultant elevation of intra-axoplasmic calcium concentration. These axoplasmic changes were indistinguishable from the axoplasmic alteration occurring in the distal portions of transpected neurites during Wallerian degeneration. The findings support the view that abnormal calcium influxes are determinants in the degeneration of peripheral nerve.