A role for voltage-gated potassium channels in the outgrowth of retinal axons in the developing visual system

Neural activity is important for establishing proper connectivity in the de veloping visual system. Tetrodotoxin blockade of sodium (Na+)-dependent act ion potentials impairs the refining of synaptic connections made by develop ing retinal ganglion cells (RGCs), but does not affect their ability to get out to their target. Although this may suggest neural activity is not requ ired for the directed extension of RGC axons, in many species developing RG Cs express additional, Na+-independent ionic mechanisms. To test whether th e ability of RGC axons to extend in a directed fashion is influenced by mem brane excitability, we blocked the principal modulators of the neural activ ity of a neuron, voltage-dependent potassium (Kv) channels. First, we showe d that RGCs and their growth cones express Kv channels when they are growin g through the brain on the way to their main midbrain target, the optic tec tum. Second, a Kv channel blocker, 4-aminopyridine (4-AP), was applied to t he developing Xenopus optic projection. Blocking Kv channels inhibited RGC axon extension and caused aberrant routing of many RGC fibers. With the hig her doses, <25% of embryos had a normal optic projection. These data sugges t that Kv channel activity regulates the guidance of growing axons in the v ertebrate brain.