MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis

Cell. 2001 Jan 26;104(2):217-31. doi: 10.1016/s0092-8674(01)00207-0.


The subthreshold, voltage-gated potassium channel of skeletal muscle is shown to contain MinK-related peptide 2 (MiRP2) and the pore-forming subunit Kv3.4. MiRP2-Kv3.4 channels differ from Kv3.4 channels in unitary conductance, voltage-dependent activation, recovery from inactivation, steady-state open probability, and block by a peptide toxin. Thus, MiRP2-Kv3.4 channels set resting membrane potential (RMP) and do not produce afterhyperpolarization or cumulative inactivation to limit action potential frequency. A missense mutation is identified in the gene for MiRP2 (KCNE3) in two families with periodic paralysis and found to segregate with the disease. Mutant MiRP2-Kv3.4 complexes exhibit reduced current density and diminished capacity to set RMP. Thus, MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11
  • Cnidarian Venoms / pharmacology
  • Cricetinae
  • Electrophysiology
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism*
  • Mutation, Missense / genetics
  • Oocytes / metabolism
  • Paralyses, Familial Periodic / genetics*
  • Paralyses, Familial Periodic / physiopathology
  • Patch-Clamp Techniques
  • Pedigree
  • Potassium Channels / genetics*
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Protein Subunits
  • Rats
  • Shaw Potassium Channels
  • Xenopus Proteins*
  • Xenopus laevis


  • BDS II protein, Anemonia sulcata
  • Cnidarian Venoms
  • KCNC4 protein, Xenopus
  • KCNC4 protein, human
  • KCNE3 protein, human
  • Kcnc4 protein, mouse
  • Kcnc4 protein, rat
  • Kcne3 protein, mouse
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Protein Subunits
  • Shaw Potassium Channels
  • Xenopus Proteins