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J Physiol Volume 586, Number 17, 4069-4089, September 1, 2008 DOI: 10.1113/jphysiol.2008.155077
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NEUROSCIENCE

Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formation

 James J. P. Alix1, Annette C. Dolphin2 and Robert Fern1

1 Department of Cell Physiology & Pharmacology, University of Leicester, Leicester, UK
2 Department of Pharmacology, University College London, London, UK

P/Q-type calcium channels are known to form clusters at the presynaptic membrane where they mediate calcium influx, triggering vesicle fusion. We now report functional P/Q channel clusters in the axolemma of developing central axons that are also associated with sites of vesicle fusion. These channels were activated by axonal action potentials and the resulting calcium influx is well suited to mediate formation of a synaptic style SNARE complex involving SNAP-25, that we show to be located on the axolemma. Vesicular elements within axons were found to be the sole repository of vesicular glutamate in developing white matter. The axonal vesicular elements expressed the glutamate transporter V-ATPase, which is responsible for vesicular glutamate loading. The P/Q channel {alpha}1A subunit was found to be present within the axolemma at early nodes of Ranvier and deleterious mutations of the {alpha}1A subunit, or an associated {alpha}2{delta}-2 subunit, disrupted the localization of nodal proteins such as voltage-gated sodium channels, β IV spectrin and CASPR-1. This was associated with the presence of malformed nodes of Ranvier characterized by an accumulation of axoplasmic vesicles under the nodal membrane. The data are consistent with the presence of a vesicular signalling pathway between axons and glial cells that is essential for proper development of the node of Ranvier.

(Received 11 April 2008; accepted after revision 27 June 2008; first published online 3 July 2008)
Corresponding author R. Fern: Department of Cell Physiology & Pharmacology, University of Leicester, PO Box 138, University Road, Leicester LE1 9HN, UK. Email: rf34{at}le.ac.uk

This paper has online supplemental material.






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