Changes in Na(+) channel expression and nodal persistent Na(+) currents associated with peripheral nerve regeneration in mice.
Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na(+) channels as well as nodal persistent Na(+) currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week. Two weeks after crush, there was a prominent increase in the number of Na(+) channel clusters per unit area, and binary or broad Na(+) channel clusters were frequently found. Excess Na(+) channel clusters were retained up to 20 weeks post-injury. Excitability testing using latent addition suggested that nodal persistent Na(+) currents markedly increased beginning at week 3, and remained through week 10. These results suggest that axonal regeneration is associated with persistently increased axonal excitability resulting from increases in the number and conductance of Na(+) channels.
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Miho
M
Nakata
Hiroko
H
Baba
Kazuaki
K
Kanai
Tomiko
T
Hoshi
Setsu
S
Sawai
Takamichi
T
Hattori
Satoshi
S
Kuwabara
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D007150:Immunohistochemistry; D051663:Kv1.2 Potassium Channel / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009409:Nerve Crush; D009410:Nerve Degeneration / Q000503:physiopathology; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology*; D010525:Peripheral Nerves / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D012584:Sciatic Nerve / Q000473:pathology; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014855:Wallerian Degeneration / Q000503:physiopathology
D051663:Kv1.2 Potassium Channel; D015221:Potassium Channels; D015222:Sodium Channels