MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.
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.
Abbott
G W
GW
Departments of Pediatrics and Cellular, Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536, USA.
Butler
M H
MH
Bendahhou
S
S
Dalakas
M C
MC
Ptacek
L J
LJ
Goldstein
S A
SA
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003064:Cnidarian Venoms / Q000494:pharmacology; D006224:Cricetinae; D004594:Electrophysiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018482:Muscle, Skeletal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D020125:Mutation, Missense / Q000235:genetics; D009865:Oocytes / Q000378:metabolism; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051381:Rats; D051670:Shaw Potassium Channels; D029867:Xenopus Proteins; D014982:Xenopus laevis
C072544:BDS II protein, Anemonia sulcata; D003064:Cnidarian Venoms; C492016:KCNC4 protein, Xenopus; C492015:KCNC4 protein, human; C418492:KCNE3 protein, human; C115399:Kcnc4 protein, mouse; C492014:Kcnc4 protein, rat; C498827:Kcne3 protein, mouse; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D021122:Protein Subunits; D051670:Shaw Potassium Channels; D029867:Xenopus Proteins