Cited by 112Ion channel regulation and functionCardiac electrophysiology and arrhythmiasPotassium and Related Disorders

Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K current

Ruff, Robert L.·1999·Neurology

Abstract

OBJECTIVE: To define how insulin acts in hypokalemic periodic paralysis (HypoPP). BACKGROUND: HypoPP results from point mutations of the skeletal muscle L-type Ca2+ channel. Attacks of flaccid paralysis are associated with hypokalemia and triggered by insulin. A persistent inward current causes depolarization-induced paralysis. The relationships of the Ca2+ channel mutations to the persistent inward current and how insulin triggers paralytic attacks are not yet known. METHODS: Intercostal muscle fibers from HypoPP and normal subjects were studied in vitro at 37 degrees C using two electrodes to determine action potential thresholds and a three-electrode voltage clamp to study membrane currents. RESULTS: HypoPP fibers were depolarized in bathing solution with 4 mM K+. Reducing K+ from 4.0 mM to 2.5 or 1.0 mM depolarized HypoPP fibers but hyperpolarized normal fibers. Adding 12 mU/mL of insulin to bathing fluids increased the depolarization of HypoPP fibers and increased the hyperpolarization of normal fibers. Depolarized HypoPP had increased action potential thresholds. The fraction of excitable muscle fibers decreased with increasing fiber depolarization. Blocking Na+ channels or L-type Ca2+ channels did not prevent depolarization induced by hypokalemia or by insulin. Insulin reduced the conductance of the inward rectifier K+ channel for outward-flowing currents. CONCLUSIONS: Insulin potentiates depolarization of hypokalemic periodic paralysis (HypoPP) fibers by reducing inward rectifier K+ conductance. The Ca2+ mutations in HypoPP indirectly derange membrane excitability by altering the function of other membrane channels.

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Crossref · 10.1212/wnl.53.7.1556

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Authors
Ruff, R. L.
Affiliations
University Hospitals of Cleveland (US)
Corresponding author
Ruff, Robert L.
Venue
Neurology
Published
1999-10-22
Volume
53
Issue
7
Pages
1556-1556
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W1967798714
Cited by
112
References
39
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 4 · 2017: 6 · 2015: 3 · 2014: 7 · 2013: 6 · 2012: 6
FWCI
2.05
Type
journal article
Language
en
Open access
closed
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
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
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Potassium and Related Disorders
Keywords
hypokalemic periodic paralysis, insulin, inwardly rectifying potassium channels, hypokalemia, action potential threshold, muscle excitability
MeSH terms
Adult, Electric Conductivity, Electrophysiology, Extracellular Space, Humans, Insulin, Male, Membrane Potentials, Potassium, Potassium Channels, Muscle Fibers, Skeletal, Hypokalemic Periodic Paralysis, Potassium Channel Blockers

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