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- Title
Stimulation-induced Ca<sup>2+</sup> influx at nodes of Ranvier in mouse peripheral motor axons.
- Authors
Zhang, Zhongsheng; David, Gavriel
- Abstract
Key points In peripheral myelinated axons of mammalian spinal motor neurons, Ca2+ influx was thought to occur only in pathological conditions such as ischaemia., Using Ca2+ imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [Ca2+] around nodes of Ranvier., These stimulation-induced [Ca2+] elevations require Ca2+ influx, and are partially reduced by blocking T-type Ca2+ channels (e.g. mibefradil) and by blocking the Na+/Ca2+ exchanger (NCX), suggesting an important contribution of Ca2+ influx via reverse-mode NCX activity., Acute disruption of paranodal myelin dramatically increases stimulation-induced [Ca2+] elevations around nodes by allowing activation of sub-myelin L-type (nimodipine-sensitive) Ca2+ channels., The Ca2+ that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca2+ influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases., Abstract Activity-dependent Ca2+ signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca2+] indicator revealed that during repetitive action potential stimulation, [Ca2+] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca2+] elevations (∼0.1 μ m with stimulation at 50 Hz, 10 s) were blocked by removal of Ca2+ from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca2+ channels and reverse mode Na+/Ca2+ exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca2+] elevations, which now included a prominent contribution from L-type Ca2+ channels. These results suggest that the peri-nodal axolemma of motor axons includes multiple pathways for stimulation-induced Ca2+ 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 [Ca2+] elevations measured in intact motor axons might mediate local responses to axonal activation. The larger [Ca2+] elevations measured after myelin disruption might, over time, contribute to the axonal degeneration observed in peripheral demyelinating neuropathies.
- Subjects
NEURAL stimulation; CALCIUM ions; NODES of Ranvier; AXONS; MOTOR neurons; LABORATORY mice; ACTION potentials
- Publication
Journal of Physiology, 2016, Vol 594, Issue 1, p39
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/JP271207