The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis
Open accessAbstract
BACKGROUND: Several missense mutations of CACNA1S and SCN4A genes occur in hypokalemic periodic paralysis. These mutations affect arginine residues in the S4 voltage sensors of the channel. Approximately 20% of cases remain genetically undefined. METHODS: We undertook direct automated DNA sequencing of the S4 regions of CACNA1S and SCN4A in 83 cases of hypokalemic periodic paralysis. RESULTS: We identified reported CACNA1S mutations in 64 cases. In the remaining 19 cases, mutations in SCN4A or other CACNA1S S4 segments were found in 10, including three novel changes and the first mutations in channel domains I (SCN4A) and III (CACNA1S). CONCLUSIONS: All mutations affected arginine residues, consistent with the gating pore cation leak hypothesis of hypokalemic periodic paralysis. Arginine mutations in S4 segments underlie 90% of hypokalemic periodic paralysis cases.
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“Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia, leading to paradoxical depolarization with consequent inactivation of Na+ channel and muscle inexcitability [20].”
From Thyrotoxic Periodic Paralysis: Clinical Challenges (2014) · cites this paper as [20]
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“Loss of function of Kir2.6 together with increased activity of Na+/K+ ATPase may trigger a positive feed-forward cycle of hypokalemia.”
From Thyrotoxic Periodic Paralysis: Clinical Challenges (2014) · cites this paper as [20]
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Citations
Cites
Dihydropyridine receptor mutations cause hypokalemic periodic paralysis
Ptáček, L. J. (1994) · Cell · doi:10.1016/0092-8674(94)90135-x · Cited by 426
A calcium channel mutation causing hypokalemic periodic paralysis
Jurkat‐Rott, K., Lehmann‐Horn, F., Elbaz, A., Heine, R., Gregg, R. G., Hogan, K. J., Powers, P. A., Laple, P., Vale-Santos, J., Weissenbach, J., et al. (1994) · Human Molecular Genetics · doi:10.1093/hmg/3.8.1415 · Cited by 315
Gating pore current in an inherited ion channelopathy
Sokolov, S., Scheuer, T., & Catterall, W. A. (2007) · Nature · doi:10.1038/nature05598 · Cited by 302
Cha, A., Ruben, P. C., George, A. L., Fujimoto, E., & Bezanilla, F. (1999) · Neuron · doi:10.1016/s0896-6273(00)80680-7 · Cited by 278
Jurkat‐Rott, K., Mitrović, N., Hang, C., Kouzmenkine, A., Iaizzo, P. A., Herzog, J., Lerche, H., Nicole, S., Vale-Santos, J., Chauveau, D., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.17.9549 · Cited by 262
Correlating phenotype and genotype in the periodic paralyses
Miller, T. M., Dias-da-Silva, M. R., Miller, H. A., Kwieciński, H., Mendell, J. R., Tawil, R., McManis, P. G., Griggs, R. C., Angelini, C. I., Servidei, S., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000143383.91137.00 · Cited by 259
Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita
Ptáček, L. J., George, A. L., Barchi, R. L., Griggs, R. C., Riggs, J. E., Robertson, M. A., & Leppert, M. (1992) · Neuron · doi:10.1016/0896-6273(92)90203-p · Cited by 245
Fontaine, B., Vale-Santos, J., Jurkat‐Rott, K., Reboul, J., Plassart, E., Rime, C.-S., Elbaz, A., Heine, R., Guimarães, J., Weissenbach, J., et al. (1994) · Nature Genetics · doi:10.1038/ng0394-267 · Cited by 233
Histidine Scanning Mutagenesis of Basic Residues of the S4 Segment of the Shaker K+ Channel
Starace, D. M., & Bezanilla, F. (2001) · The Journal of General Physiology · doi:10.1085/jgp.117.5.469 · Cited by 232
Sternberg, D. (2001) · Brain · doi:10.1093/brain/124.6.1091 · Cited by 214
PATHOMECHANISMS IN CHANNELOPATHIES OF SKELETAL MUSCLE AND BRAIN
Cannon, S. C. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112815 · Cited by 210
A novel sodium channel mutation in a family with hypokalemic periodic paralysis
Bulman, D. E., Scoggan, K. A., van Oene, M. D., Nicolle, M. W., Hahn, A. F., Tollar, L. L., & Ebers, G. C. (1999) · Neurology · doi:10.1212/wnl.53.9.1932 · Cited by 191
Jurkat‐Rott, K., Weber, M. D., Fauler, M., Guo, X.-H., Holzherr, B. D., Paczulla, A., Nordsborg, N. B., Jöechle, W., & Lehmann‐Horn, F. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811277106 · Cited by 172
Struyk, A. F., & Cannon, S. C. (2007) · The Journal of General Physiology · doi:10.1085/jgp.200709755 · Cited by 170
Insulin acts in hypokalemic periodic paralysis by reducing inward rectifier K current
Ruff, R. L. (1999) · Neurology · doi:10.1212/wnl.53.7.1556 · Cited by 112
Tricarico, D., Servidei, S., Tonali, P., Jurkat‐Rott, K., & Camerino, D. C. (1999) · Journal of Clinical Investigation · doi:10.1172/jci4552 · Cited by 108
Fouad, G. T., Dalakas, M. C., Servidei, S., Mendell, J. R., den Bergh, P. Y. K. V., Angelini, C. I., Alderson, K., Griggs, R. C., Tawil, R., Gregg, R. G., et al. (1997) · Neuromuscular Disorders · doi:10.1016/s0960-8966(96)00401-4 · Cited by 101
Struyk, A. F., & Cannon, S. C. (2007) · Muscle & Nerve · doi:10.1002/mus.20928 · Cited by 78
New mutations of SCN4A cause a potassium-sensitive normokalemic periodic paralysis
Vicart, S., Sternberg, D., Fournier, E., Ochsner, F., Laforêt, P., Küntzer, T., Eymard, B., Hainque, B., & Fontaine, B. (2004) · Neurology · doi:10.1212/01.wnl.0000145768.09934.ec · Cited by 77
Kuzmenkin, A., Muncan, V., Jurkat‐Rott, K., Hang, C., Lerche, H., Lehmann‐Horn, F., & Mitrović, N. (2002) · Brain · doi:10.1093/brain/awf071 · Cited by 76
Bendahhou, S., Cummins, T., Griggs, R. C., Fu, Y., & Ptáček, L. J. (2001) · Annals of Neurology · doi:10.1002/ana.1144 · Cited by 70
Familial Alzheimer's disease: Site of mutation influences clinical phenotype
Lippa, C. F., Swearer, J. M., Kane, K., Nochlin, D., Bird, T. D., Ghetti, B. F., Nee, L. E., George‐Hyslop, P. S., Pollen, D. A., & Drachman, D. A. (2000) · Annals of Neurology · doi:10.1002/1531-8249(200009)48:3 · Cited by 67
Novel CACNA1S mutation causes autosomal dominant hypokalemic periodic paralysis in a Chinese family
Wang, Q., Liu, M., Xu, C., Tang, Z., Liao, Y., Du, R., Li, W., Wu, X., Wang, X., Liu, P., et al. (2005) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0638-4 · Cited by 50
Sodium channel gene mutations in hypokalemic periodic paralysis: An uncommon cause in the UK
Davies, N. P., Eunson, L. H., Samuel, M., & Hanna, M. G. (2001) · Neurology · doi:10.1212/wnl.57.7.1323 · Cited by 44
Self-citationKim, M., Lee, S., Park, M., Kim, B. C., Cho, K.-H., Lee, M.-C., Kim, J., & Kim, S. M. (2004) · Neuromuscular Disorders · doi:10.1016/j.nmd.2004.07.005 · Cited by 28
Sasaki, R., Takano, H., Kamakura, K., Kaida, K., Hirata, A., Saito, M., Tanaka, H., Kuzuhara, S., & Tsuji, S. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.692 · Cited by 24
Skeletal muscle sodium current is reduced in hypokalemic periodic paralysis
Ruff, R. L. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.170293197 · Cited by 19
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Review of the Diagnosis and Treatment of Periodic Paralysis
Statland, J. M., Fontaine, B., Hanna, M. G., Johnson, N. E., Kissel, J. T., Sansone, V., Shieh, P. B., Tawil, R., Trivedi, J. R., Cannon, S. C., et al. (2017) · Muscle & Nerve · doi:10.1002/mus.26009 · Cited by 274
Self-citationChannelopathies of Skeletal Muscle Excitability
Cannon, S. C. (2015) · Comprehensive physiology · doi:10.1002/cphy.c140062 · Cited by 242
Mechanism of Thyrotoxic Periodic Paralysis
Lin, S.-H., & Huang, C.-L. (2012) · Journal of the American Society of Nephrology · doi:10.1681/asn.2012010046 · Cited by 174
Sodium Channelopathies of Skeletal Muscle
Cannon, S. C. (2017) · Handbook of experimental pharmacology · doi:10.1007/164_2017_52 · Cited by 142
Predicting functional effects of missense variants in voltage-gated sodium and calcium channels
Heyne, H. O., Baez-Nieto, D., Iqbal, S., Palmer, D. S., Brunklaus, A., May, P., Collaborative, E., Johannesen, K. M., Lauxmann, S., Lemke, J. R., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay6848 · Cited by 140
Metadata
- Authors
- Matthews, E., Labrum, R., Sweeney, M. G., Sud, R., Haworth, A., Chinnery, P. F., Meola, G., Schorge, S., Kullmann, D. M., Davis, M. B., & Hanna, M. G.
- Affiliations
- University of Milan (IT)
- Venue
- Neurology
- Published
- 2009-05-05
- Volume
- 72
- Issue
- 18
- Pages
- 1544-1547
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2848101
- OpenAlex
- W2116159595
- Cited by
- 201
- References
- 27
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 7 · 2021: 16 · 2020: 11 · 2019: 19 · 2018: 13 · 2017: 13 · 2016: 11 · 2015: 12 · 2014: 10 · 2013: 12 · 2012: 9
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (084980, G0601943)
- National Institute for Health and Care Research (G0601943)
- Brain Research Trust
- University College London (G0601943)
- National Institutes of Health
- Medical Research Council (G0601943)
- National Center for Research Resources (U54RR019498, RR019498)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- hypokalemic periodic paralysis, CACNA1S, SCN4A, arginine mutations, missense mutations, voltage-gated potassium channels, novel mutations, genetic diagnosis
- MeSH terms
- Adolescent, Amino Acid Sequence, Arginine, DNA Mutational Analysis, Gene Frequency, Genetic Testing, Genotype, Humans, Membrane Potentials, Muscle Contraction, Mutation, Calcium Channels, Sodium Channels, Ion Channel Gating, Protein Structure, Tertiary, Muscle, Skeletal, Amino Acid Substitution, Genetic Predisposition to Disease, Paralysis, Hyperkalemic Periodic, Calcium Channels, L-Type, Inheritance Patterns, Young Adult, NAV1.4 Voltage-Gated Sodium Channel
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