N- and L-Type Voltage-Gated Calcium Channels Mediate Fast Calcium Transients in Axonal Shafts of Mouse Peripheral Nerve.
In the peripheral nervous system (PNS) a vast number of axons are accommodated within fiber bundles that constitute peripheral nerves. A major function of peripheral axons is to propagate action potentials along their length, and hence they are equipped with Na(+) and K(+) channels, which ensure successful generation, conduction and termination of each action potential. However little is known about Ca(2+) ion channels expressed along peripheral axons and their possible functional significance. The goal of the present study was to test whether voltage-gated Ca(2+) channels (VGCCs) are present along peripheral nerve axons in situ and mediate rapid activity-dependent Ca(2+) elevations under physiological circumstances. To address this question we used mouse sciatic nerve slices, Ca(2+) indicator Oregon Green BAPTA-1, and 2-photon Ca(2+) imaging in fast line scan mode (500 Hz). We report that transient increases in intra-axonal Ca(2+) concentration take place along peripheral nerve axons in situ when axons are stimulated electrically with single pulses. Furthermore, we show for the first time that Ca(2+) transients in peripheral nerves are fast, i.e., occur in a millisecond time-domain. Combining Ca(2+) imaging and pharmacology with specific blockers of different VGCCs subtypes we demonstrate that Ca(2+) transients in peripheral nerves are mediated mainly by N-type and L-type VGCCs. Discovery of fast Ca(2+) entry into the axonal shafts through VGCCs in peripheral nerves suggests that Ca(2+) may be involved in regulation of action potential propagation and/or properties in this system, or mediate neurotransmitter release along peripheral axons as it occurs in the optic nerve and white matter of the central nervous system (CNS).
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen Tübingen, Germany.
Ruxandra
R
Barzan
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen Tübingen, Germany.
Friederike
F
Pfeiffer
Group of Neuron Glia Interaction, Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen Tübingen, Germany.
Maria
M
Kukley
Ca2+ channels; axonal shafts; peripheral nervous system