Zhongsheng Zhang, Gavriel David

Activity-dependent Ca(2+) signaling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+) ] indicator revealed that during repetitive action potential stimulation [Ca(2+) ] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+) ] elevations (∼0.1 μm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+) /Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+) ] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These results suggest that the peri-nodal axolemma of motor axons includes multiple pathways for stimulation-induced Ca(2+) influx, some active in normally-myelinated axons (T-type channels, NCX), others active only when exposed by myelin disruption (L-type channels). The modest axoplasmic peri-nodal [Ca(2+) ] elevations measured in intact motor axons might mediate local responses to axonal activation. The larger [Ca(2+) ] elevations measured after myelin disruption might, over time, contribute to the axonal degeneration observed in peripheral demyelinating neuropathies. This article is protected by copyright. All rights reserved.