Dynamic potassium channel distributions during axonal development prevent aberrant firing patterns.
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.
Vabnick
I
I
Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, USA.
Trimmer
J S
JS
Schwarz
T L
TL
Levinson
S R
SR
Risal
D
D
Shrager
P
P
D000200:Action Potentials / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008839:Microelectrodes; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000502:physiology; D009412:Nerve Fibers / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D012584:Sciatic Nerve / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D051637:Shaker Superfamily of Potassium Channels
D015221:Potassium Channels; D051637:Shaker Superfamily of Potassium Channels