Dynamic Potassium Channel Distributions during Axonal Development Prevent Aberrant Firing Patterns

Abstract

The distribution and function of Shaker-related K+ channels were studied with immunofluorescence and electrophysiology in sciatic nerves of developing rats. At nodes of Ranvier, Na+ channel clustering occurred very early (postnatal days 1-3). Although K+ channels were not yet segregated at most of these sites, they were directly involved in action potential generation, reducing duration, and the refractory period. At approximately 1 week, K+ channel clusters were first seen but were within the nodal gap and in paranodes, and only later (weeks 2-4) were they shifted to juxtaparanodal regions. K+ channel function was most dramatic during this transition period, with block producing repetitive firing in response to single stimuli. As K+ channels were increasingly sequestered in juxtaparanodes, conduction became progressively insensitive to K+ channel block. Over the first 3 weeks, K+ channel clustering was often asymmetric, with channels exclusively in the distal paranode in approximately 40% of cases. A computational model suggested a mechanism for the firing patterns observed, and the results provide a role for K+ channels in the prevention of aberrant excitation as myelination proceeds during development.