The Journal of Neuroscience, February 1, 2000, 20(3):1020-1029
A Role for Voltage-Gated Potassium Channels in the Outgrowth of
Retinal Axons in the Developing Visual System
Sarah
McFarlane and
Natashka S.
Pollock
University of Calgary, Department of Cell Biology and Anatomy,
Calgary, Alberta T2N 4N1, Canada
Neural activity is important for establishing proper connectivity
in the developing visual system. Tetrodotoxin blockade of sodium
(Na+)-dependent action potentials impairs the
refining of synaptic connections made by developing retinal ganglion
cells (RGCs), but does not affect their ability to get out to their
target. Although this may suggest neural activity is not required for the directed extension of RGC axons, in many species developing RGCs
express additional, Na+-independent ionic
mechanisms. To test whether the ability of RGC axons to extend in a
directed fashion is influenced by membrane excitability, we blocked the
principal modulators of the neural activity of a neuron,
voltage-dependent potassium (Kv) channels. First, we showed that RGCs
and their growth cones express Kv channels when they are growing
through the brain on the way to their main midbrain target, the optic
tectum. Second, a Kv channel blocker, 4-aminopyridine (4-AP), was
applied to the developing Xenopus optic projection.
Blocking Kv channels inhibited RGC axon extension and caused aberrant
routing of many RGC fibers. With the higher doses, <25% of embryos
had a normal optic projection. These data suggest that Kv channel
activity regulates the guidance of growing axons in the vertebrate brain.
Key words:
axon guidance; Xenopus; target recognition; growth cone; electrical activity; neurite outgrowth; voltage-dependent
potassium channels
Copyright © 2000 Society for Neuroscience 0270-6474/00/2031020-10$05.00/0