Nav 1.4 slow-inactivation: is it a player in the warm-up phenomenon of myotonic disorders?

Muscle Nerve. 2013 Apr;47(4):483-7. doi: 10.1002/mus.23713. Epub 2013 Feb 4.

Abstract

Myotonia is a heritable disorder in which patients are unable to willfully relax their muscles. The physiological basis for myotonia lies in well-established deficiencies of skeletal muscle chloride and sodium conductances. What is unclear is how normal muscle function can temporarily return with repeated movement, the so-called "warm-up" phenomenon. Electrophysiological analyses of the skeletal muscle voltage-gated sodium channel Nav 1.4 (gene name SCN4A), a key player in myotonia, have revealed several parallels between the Nav 1.4 biophysical signature, specifically slow-inactivation, and myotonic warm-up, which suggest that Nav 1.4 is critical not only in producing the myotonic reaction, but also in mediating the warm-up.

MeSH terms

  • Chloride Channels / metabolism
  • Humans
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Myotonia / metabolism*
  • Myotonia / physiopathology
  • Myotonic Disorders / metabolism*
  • Myotonic Disorders / physiopathology
  • NAV1.4 Voltage-Gated Sodium Channel / genetics
  • NAV1.4 Voltage-Gated Sodium Channel / metabolism*

Substances

  • CLC-1 channel
  • Chloride Channels
  • NAV1.4 Voltage-Gated Sodium Channel
  • SCN4A protein, human