Cited by 294Ion channel regulation and functionCardiac electrophysiology and arrhythmiasIon Transport and Channel Regulation

MiRP2 Forms Potassium Channels in Skeletal Muscle with Kv3.4 and Is Associated with Periodic Paralysis

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Abbott, Geoffrey W, Butler, Margaret H, Bendahhou, Saïd, Dalakas, Marinos C, Ptacek, Louis J, Goldstein, Steve A.N·2001·Cell

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.

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Crossref · 10.1016/s0092-8674(01)00207-0

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  • The MiRP2-Kv3.4 mutation reduces potassium efflux, resulting in hypokalemia, which decreases muscle membrane excitability and leads to muscle weakness and paralysis.

    “The MiRP2-Kv3.4 mutation reduces potassium efflux, resulting in hypokalemia. This condition decreases muscle membrane excitability, leading to muscle weakness and paralysis [19].”

    From Thyrotoxic Hypokalemic Periodic Paralysis: Pathophysiological Mechanisms (2025) · cites this paper as [19]

    The R83H-MiRP2 mutation section (page unavailable) reports reduced outward current density and an association with paralytic weakness. The discussion (page unavailable) links periodic paralysis to altered muscle resting potential and excitability, but does not say that reduced potassium efflux causes hypokalemia or that hypokalemia drives the weakness. It describes the associated presentations as unlike classical hypokalemic periodic paralysis. (LLM, conf=0.87)

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  1. phoresis as single-strand conformation polymorphisms. Proc. Natl.

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Authors
Abbott, G. W., Butler, M. H., Bendahhou, S., Dalakas, M. C., Ptacek, L. J., & Goldstein, S. A. N.
Affiliations
  • Yale University (US)
  • National Institutes of Health (US)
Corresponding author
Goldstein, Steve A.N
Venue
Cell
Publisher
Elsevier BV
Published
2001-01
Volume
104
Issue
2
Pages
217-231
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2069886131
Cited by
294
References
57
Citations by year
2026: 7 · 2025: 8 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 5
FWCI
11.64
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
National Center for Research Resources (MO1-RR-00064, M01RR000064)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
KCNE3, Kv3.4, voltage-gated potassium channels, skeletal muscle, periodic paralysis, resting membrane potential, single-channel conductance, channel inactivation
MeSH terms
Animals, Cell Line, Cell Membrane, Chromosome Mapping, Chromosomes, Human, Pair 11, Cnidarian Venoms, Electrophysiology, Female, Cricetinae, Humans, Immunohistochemistry, Male, Membrane Potentials, Oocytes, Paralyses, Familial Periodic, Pedigree, Xenopus laevis, Potassium Channels, Patch-Clamp Techniques, Muscle, Skeletal, Mutation, Missense, Protein Subunits, Potassium Channels, Voltage-Gated, Xenopus Proteins, Mice, Rats, Shaw Potassium Channels

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