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 ∼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 ∼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.