Abstract
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
Substances
-
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