Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K current
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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Insulin and catecholamines not only activate Na+, K+-ATPase but may also inhibit inward rectifying K+ (Kir) channels.
“In fact, insulin and catecholamines not only activate Na+, K+-ATPase but may also inhibit inward rectifying K+ (Kir) channels (39).”
From A 10-year analysis of thyrotoxic periodic paralysis in 135 patients: focus on symptomatology and precipitants (2013) · cites this paper as [39]
Insulin and catecholamine not only activate Na+/K+ ATPase but also inhibit Kir channels.
“Moreover, insulin and catecholamine not only activate Na+/K+ ATPase but also inhibit Kir channels [17].”
From Thyrotoxic Periodic Paralysis: Clinical Challenges (2014) · cites this paper as [17]
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Fifty years of gating currents and channel gating
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Thyrotoxic periodic paralysis triggered by β2- adrenergic bronchodilators
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Non-dystrophic Myotonias And Periodic Paralyses
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A single-center retrospective study on the clinical features of thyrotoxic periodic paralysis
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Paralysie périodique thyréotoxique hypokaliémique : quatre observations et revue de la littérature
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An atypical CaV1.1 mutation reveals a common mechanism for hypokalemic periodic paralysis
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Mechanisms underlying the distinct K+ dependencies of periodic paralysis
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An important piece has been placed in the puzzle of hypokalemic periodic paralysis
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Self-citationThe spectrum of neuromuscular diseases with tubular aggregates
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Electrophysiology and molecular pharmacology of muscle channelopathies
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Sour on the inside, calm on the outside: How acetazolamide may stabilize membrane excitability
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Chapter 23 Skeletal muscle channelopathies: myotonias, periodic paralyses and malignant hyperthermia
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Cav1.1 Channel and Hypokalemic Periodic Paralysis
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Channelopathies; Clinical Manifestations
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New territory opened by periodic paralysis associated with mitochondrial DNA mutation
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A case of type 2 diabetes manifested by hypokalemic periodic paralysis
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THYROTOXIC PERIODIC PARALYSIS: A CASE REPORT AND REVIEW OF LITERATURE
Choudhuri, R., Adhikari, D., Kar, S. K., & Mitra, S. (2014)
Hypokalemic thyrotoxic periodic paralysis in a young Serbian male
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- Authors
- Ruff, R. L.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Ruff, Robert L.
- ORCID
- 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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