The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
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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In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
Dihydropyridine receptor mutations cause hypokalemic periodic paralysis
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A calcium channel mutation causing hypokalemic periodic paralysis
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Self-citationElbaz, A., Vale-Santos, J., Jurkat‐Rott, K., Lapie, P., Ophoff, R. A., Bady, B., Links, T. P., Piussan, C., Vila, A., & Monnier, N. (1995) · Europe PMC (PubMed Central) · Cited by 113
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- Ruff RL. Insulin potentiates hypokalemic periodic paralysis by reducing inward rectifier K current, not by opening an L-type Ca channel. Neurology 1998;50 (suppl 4):A367. Abstract.
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Self-citationParálisis periódica hipocalémica: reporte de caso.
Reyes, R., Culma, L. A. R., & Mur, R. M. (2020) · Revista Ecuatoriana de Neurologia · doi:10.46997/revecuatneurol29300097
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Frequency of Hyperthyroidism in Hypokalemic Periodic Paralysis
Lakho, M. A., Magsi, A. G., Lakho, S., Ali, M. M., Bhanbhro, F. I., & Magsi, S. A. (2022) · Pakistan Journal of Medical and Health Sciences · doi:10.53350/pjmhs22166353
Secondary Hypokalemic Periodic Paralysis - a review of literature
Pina, H., Balhana, S., Machete, M., Noronha, C., Aragüés, J. M., Guerra, S., & Valadas, C. (2023) · Revista Portuguesa de Endocrinologia Diabetes e Metabolismo · doi:10.26497/ar220026
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Wouters, C., Willems, M., Mullens, A., & Meersman, A. (2023) · Emergency Medicine - Open Journal · doi:10.17140/emoj-9-172
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Denman, K., & Rich, M. M. (2026) · Muscle & Nerve · doi:10.1002/mus.70158
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Self-citation
Metadata
- 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 › Nephrology › 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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