Stimulation-induced Ca2+ influx at nodes of Ranvier in mouse peripheral motor axons

Zhongsheng Zhang, Gavriel David

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 μm 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.

Original languageEnglish (US)
Pages (from-to)39-57
Number of pages19
JournalJournal of Physiology
Volume594
Issue number1
DOIs
StatePublished - Jan 1 2016

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Ranvier's Nodes
Axons
Myelin Sheath
Phrenic Nerve
Lysophosphatidylcholines
Spinal Nerve Roots
Carisoprodol
Motor Neurons
Peripheral Nervous System Diseases
Action Potentials
Pharmacology

ASJC Scopus subject areas

  • Physiology

Cite this

Stimulation-induced Ca2+ influx at nodes of Ranvier in mouse peripheral motor axons. / Zhang, Zhongsheng; David, Gavriel.

In: Journal of Physiology, Vol. 594, No. 1, 01.01.2016, p. 39-57.

Research output: Contribution to journalArticle

Zhang, Zhongsheng ; David, Gavriel. / Stimulation-induced Ca2+ influx at nodes of Ranvier in mouse peripheral motor axons. In: Journal of Physiology. 2016 ; Vol. 594, No. 1. pp. 39-57.
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