Dynamic potassium channel distributions during axonal development prevent aberrant firing patterns

The distribution and function of Shaker-related K+ channels were studied wi th immunofluorescence and electrophysiology in sciatic nerves of developing rats. At nodes of Ranvier, Na+ channel clustering occurred very early (pos tnatal days 1-3). Although K+ channels were not yet segregated at most of t hese sites, they were directly involved in action potential generation, red ucing duration, and the refractory period. At similar to 1 week, K+ channel clusters were first seen but were within the nodal gap and in paranodes, a nd only later (weeks 2-4) were they shifted to juxtaparanodal regions. K+ c hannel 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 progress ively insensitive to K+ channel block. Over the first 3 weeks, K+ channel c lustering was often asymmetric, with channels exclusively in the distal par anode in similar to 40% of cases. A computational model suggested a mechani sm for the firing patterns observed, and the results provide a role for Kchannels in the prevention of aberrant excitation as myelination proceeds d uring development.