Skip to main content

Advertisement

Springer Nature Link
Log in

Skeletal muscle ClC-1 chloride channels in health and diseases

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

In 1970, the study of the pathomechanisms underlying myotonia in muscle fibers isolated from myotonic goats highlighted the importance of chloride conductance for skeletal muscle function; 20 years later, the human ClC-1 chloride channel has been cloned; last year, the crystal structure of human protein has been solved. Over the years, the efforts of many researchers led to significant advances in acknowledging the role of ClC-1 in skeletal muscle physiology and the mechanisms through which ClC-1 dysfunctions lead to impaired muscle function. The wide spectrum of pathophysiological conditions associated with modification of ClC-1 activity, either as the primary cause, such as in myotonia congenita, or as a secondary adaptive mechanism in other neuromuscular diseases, supports the idea that ClC-1 is relevant to preserve not only for skeletal muscle excitability, but also for skeletal muscle adaptation to physiological or harmful events. Improving this understanding could open promising avenues toward the development of selective and safe drugs targeting ClC-1, with the aim to restore normal muscle function. This review summarizes the most relevant research on ClC-1 channel physiology, associated diseases, and pharmacology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Accardi A, Pusch M (2000) Fast and slow gating relaxations in the muscle chloride channel ClC-1. J Gen Physiol 116:433–444. https://doi.org/10.1085/jgp.116.3.433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Agus V, Di Silvio A, Rolland JF, Mondini A, Tremolada S, Montag K, Scarabottolo L, Redaelli L, Lohmer S (2015) Bringing the light to high throughput screening: use of optogenetic tools for the development of recombinant cellular assays. Progress in Biomedical Optics and Imaging - Proceedings of SPIEVolume 9305, 2015, Article number 93052T Optical Techniques in Neurosurgery, Neurophotonics, and Optogenetics II; San Francisco; United States

  3. Altamura C, Lucchiari S, Sahbani D, Ulzi G, Comi GP, D’Ambrosio P, Petillo R, Politano L, Vercelli L, Mongini T, Dotti MT, Cardani R, Meola G, Lo Monaco M, Matthews E, Hanna MG, Carratù MR, Conte D, Imbrici P, Desaphy JF (2018) The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel. Hum Mutat 39(9):1273–1283. https://doi.org/10.1002/humu.23581

    Article  CAS  PubMed  Google Scholar 

  4. Altamura C, Mangiatordi GF, Nicolotti O, Sahbani D, Farinato A, Leonetti F, Carratù MR, Conte D, Desaphy JF, Imbrici P (2018) Mapping ligand binding pockets in chloride ClC-1 channels through an integrated in silico and experimental approach using anthracene-9-carboxylic acid and niflumic acid. Br J Pharmacol 175(10):1770–1780. https://doi.org/10.1111/bph.14192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Andersen G, Hedermann G, Witting N, Duno M, Andersen H, Vissing J (2017) The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study. Brain 140(9):2295–2305. https://doi.org/10.1093/brain/awx192

    Article  PubMed  Google Scholar 

  6. Arnold WD, Kline D, Sanderson A, Hawash AA, Bartlett A, Novak KR, Rich MM, Kissel JT (2017) Open-label trial of ranolazine for the treatment of myotonia congenita. Neurology 89(7):710–713. https://doi.org/10.1212/WNL.0000000000004229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aromataris EC, Astill DS, Rychkov GY, Bryant SH, Bretag AH, Roberts ML (1999) Modulation of the gating of CIC-1 by S-(−) 2-(4-chlorophenoxy) propionic acid. Br J Pharmacol 126:1375–1382

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bennetts B, Parker MW (2013) Molecular determinants of common gating of a ClC chloride channel. Nat Commun 4:2507. https://doi.org/10.1038/ncomms3507

    Article  CAS  PubMed  Google Scholar 

  9. Bennetts B, Parker MW, Cromer BA (2007) Inhibition of skeletal muscle ClC-1 chloride channels by low intracellular pH and ATP. J Biol Chem 282:32780–32791

    CAS  PubMed  Google Scholar 

  10. Bennetts B, Yu Y, Chen TY, Parker MW (2012) Intracellular β-nicotinamide adenine dinucleotide inhibits the skeletal muscle ClC-1 chloride channel. J Biol Chem 287:25808–25820

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Brugnoni R, Kapetis D, Imbrici P, Pessia M, Canioni E, Colleoni L, de Rosbo NK, Morandi L, Cudia P, Gashemi N, Bernasconi P, Desaphy JF, Conte D, Mantegazza R (2013) A large cohort of myotonia congenita probands: novel mutations and a high-frequency mutation region in exons 4 and 5 of the CLCN1 gene. J Hum Genet 58:581–587

    CAS  PubMed  Google Scholar 

  12. Bryant SH, Morales-Aguilera A (1971) Chloride conductance in normal and myotonic muscle fibres and the action of monocarboxylic aromatic acids. J Physiol 219:367–383

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Bryant SH, Conte-Camerino D (1991) Chloride channel regulation in the skeletal muscle of normal and myotonic goats. Pflugers Arch 417:605–610

    CAS  PubMed  Google Scholar 

  14. Camerino GM, Bouchè M, De Bellis M, Cannone M, Liantonio A, Musaraj K et al (2014) Protein kinase C theta (PKCθ) modulates the ClC-1 chloride channel activity and skeletal muscle phenotype: a biophysical and gene expression study in mouse models lacking the PKCθ. Pflugers Arch 466:2215–2228. https://doi.org/10.1007/s00424-014-1495-1

    Article  CAS  PubMed  Google Scholar 

  15. Camerino GM, Fonzino A, Conte E, De Bellis M, Mele A, Liantonio A, Tricarico D, Tarantino N, Dobrowolny G, Musarò A, Desaphy JF, De Luca A, Pierno S (2019) Elucidating the contribution of skeletal muscle ion channels to amyotrophic lateral sclerosis in search of new therapeutic options. Sci Rep 9(1):3185. https://doi.org/10.1038/s41598-019-39676-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cardani R, Giagnacovo M, Botta A, Rinaldi F, Morgante A, Udd B, Raheem O, Penttilä S, Suominen T, Renna LV, Sansone V, Bugiardini E, Novelli G, Meola G (2012) Co-segregation of DM2 with a recessive CLCN1 mutation in juvenile onset of myotonic dystrophy type 2. J Neurol 259:2090–2099. https://doi.org/10.1007/s00415-012-6462-1

    Article  CAS  PubMed  Google Scholar 

  17. Cederholm JM, Rychkov GY, Bagley CJ, Bretag AH (2010) Inter-subunit communication and fast gate integrity are important for common gating in hClC-1. Int J Biochem Cell Biol 42:1182–1188

    CAS  PubMed  Google Scholar 

  18. Charlet-B N, Savkur RS, Singh G, Philips AV, Grice EA, Cooper TA (2002) Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 10(1):45–53

    CAS  PubMed  Google Scholar 

  19. Chen TT, Klassen TL, Goldman AM, Marini C, Guerrini R, Noebels JL (2013) Novel brain expression of ClC-1 chloride channels and enrichment of CLCN1 variants in epilepsy. Neurology 80:1078–1085. https://doi.org/10.1212/WNL.0b013e31828868e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Chen W, Wang Y, Abe Y, Cheney L, Udd B, Li YP (2007) Haploinsufficiency for Znf9 in Znf9+/− mice is associated with multiorgan abnormalities resembling myotonic dystrophy. J Mol Biol 368:8–17

    CAS  PubMed  Google Scholar 

  21. Chen YA, Peng YJ, Hu MC, Huang JJ, Chien YC, Wu JT, Chen TY, Tang CY (2015) The cullin 4A/B-DDB1-cereblon E3 ubiquitin ligase complex mediates the degradation of CLC-1 chloride channels. Sci Rep 5:10667. https://doi.org/10.1038/srep10667

    Article  PubMed  PubMed Central  Google Scholar 

  22. Colding-Jørgensen E (2005) Phenotypic variability in myotonia congenita. Muscle Nerve 32:19–34

    PubMed  Google Scholar 

  23. Conte Camerino D, De Luca A, Mambrini M, Vrbovà G (1989) Membrane ionic conductances in normal and denervated skeletal muscle of the rat during development. Pflugers Arch 413:568–570

    CAS  PubMed  Google Scholar 

  24. Cozzoli A, Liantonio A, Conte E, Cannone M, Massari AM, Giustino A, Scaramuzzi A, Pierno S, Mantuano P, Capogrosso RF, Camerino GM, de Luca A (2014) Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase. Am J Physiol Cell Physiol 307:C634–C647. https://doi.org/10.1152/ajpcell.00372.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. De Bellis M, Sanarica F, Carocci A, Lentini G, Pierno S, Rolland JF, Conte Camerino D, De Luca A (2018) Dual action of mexiletine and its pyrroline derivatives as skeletal muscle sodium channel blockers and anti-oxidant compounds: toward novel therapeutic potential. Front Pharmacol 8:907

    PubMed  PubMed Central  Google Scholar 

  26. De Luca A, Pierno S, Camerino DC (1995) Changes of membrane electrical properties in extensor digitorum longus muscle from dystrophic (mdx) mice. Muscle Nerve 18:1196–1198

    PubMed  Google Scholar 

  27. De Luca A, Pierno S, Camerino DC (1997) Electrical properties of diaphragm and EDL muscles during the life of dystrophic mice. Am J Phys 272:C333–C340

    Google Scholar 

  28. De Luca A, Pierno S, Liantonio A, Camerino C, Conte Camerino D (1998) Phosphorylation and IGF-1-mediated dephosphorylation pathways control the activity and the pharmacological properties of skeletal muscle chloride channels. Br J Pharmacol 125:477–482

    PubMed  PubMed Central  Google Scholar 

  29. De Luca A, Tricarico D, Wagner R, Bryant SH, Tortorella V, Conte Camerino D (1992) Opposite effects of enantiomers of clofibric acid derivative on rat skeletal muscle chlorideconductance: antagonism studies and theoretical modeling of two different receptor site interactions. J Pharmacol Exp Ther 260:364–368

    PubMed  Google Scholar 

  30. De Luca A, Tricarico D, Pierno S, Conte Camerino D (1994) Aging and chloride channel regulation in rat fast-twitch muscle fibres. Pflugers Arch 427:80–85

    PubMed  Google Scholar 

  31. De Luca A, Conte Camerino D, Connold A, Vrbovà G (1990) Pharmacological block of chloride channels of developing rat skeletal muscle affects the differentiation of specific contractile properties. Pflugers Arch 416:17–21

    PubMed  Google Scholar 

  32. De Luca A, Pierno S, Cocchi D, Conte Camerino D (1997) Effects of chronic growth hormone treatment in aged rats on the biophysical and pharmacological properties of skeletal muscle chloride channels. Br J Pharmacol 121:369–374

    PubMed  PubMed Central  Google Scholar 

  33. de Paoli FV, Broch-Lips M, Pedersen TH, Nielsen OB (2013) Relationship between membrane Cl- conductance and contractile endurance in isolated rat muscles. J Physiol 591:531–545. https://doi.org/10.1113/jphysiol.2012.243246

    Article  CAS  PubMed  Google Scholar 

  34. de Paoli FV, Ørtenblad N, Pedersen TH, Jørgensen R, Nielsen OB (2010) Lactate per se improves the excitability of depolarized rat skeletal muscle by reducing the Cl- conductance. J Physiol 588:4785–4794. https://doi.org/10.1113/jphysiol.2010.196568

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Desaphy J-F, Carbonara R, Costanza T, Conte Camerino D (2014) Preclinical evaluation of marketed sodium channel blockers in a rat model of myotonia discloses new promising antimyotonic drugs. Exp Neurol 255:96–102

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Desaphy J-F, De Luca A, Pierno S, Imbrici P, Conte Camerino D (1998) Partial recovery of skeletal muscle sodium channel properties in aged rats chronically treated with growth hormone or the GH-secretagogue hexarelin. J Pharmacol Exp Ther 286:903–912

    CAS  PubMed  Google Scholar 

  37. Desaphy JF, Gramegna G, Altamura C, Dinardo MM, Imbrici P, George AL Jr, Modoni A, Lomonaco M, Conte Camerino D (2013) Functional characterization of ClC-1 mutations from patients affected by recessive myotonia congenita presenting with different clinical phenotypes. Exp Neurol 248:530–540. https://doi.org/10.1016/j.expneurol.2013.07.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Desaphy JF, Modoni A, Lomonaco M, Camerino DC (2013) Dramatic improvement of myotonia permanens with flecainide: a two-case report of a possible bench-to-bedside pharmacogenetics strategy. Eur J Clin Pharmacol 69(4):1037–1039. https://doi.org/10.1007/s00228-012-1414-3

    Article  PubMed  Google Scholar 

  39. Desaphy JF, Pierno S, Liantonio A, De Luca A, Didonna MP, Frigeri A, Nicchia GP, Svelto M, Camerino C, Zallone A, Camerino DC (2005) Recovery of the soleus muscle after short- and long-term disuse induced by hindlimb unloading: effects on the electrical properties and myosin heavy chain profile. Neurobiol Dis 18(2):356–365

    CAS  PubMed  Google Scholar 

  40. DiFranco M, Herrera A, Vergara JL (2011) Chloride currents from the transverse tubular system in adult mammalian skeletal muscle fibers. J Gen Physiol 137:21–41. https://doi.org/10.1085/jgp.201010496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Duffield M, Rychkov G, Bretag A, Roberts M (2003) Involvement of helices at the dimmer interface in ClC-1 common gating. J Gen Physiol 121:149–161

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Duno M, Colding-Jorgensen E, Grunnet M, Jespersen T, Vissing J, Schwartz M (2004) Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype. Eur J Hum Genet 12:738–743

    CAS  PubMed  Google Scholar 

  43. Dupont C, Denman KS, Hawash AA, Voss AA, Rich MM (2019) Treatment of myotonia congenita with retigabine in mice. Exp Neurol 315:52–59. https://doi.org/10.1016/j.expneurol.2019.02.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dutka TL, Murphy RM, Stephenson DG, Lamb GD (2008) Chloride conductance in the transverse tubular system of rat skeletal muscle fibres: importance in excitation–contraction coupling and fatigue. J Physiol 586(3):875–887

    CAS  PubMed  Google Scholar 

  45. Dutzler R, Campbell EB, Cadene M, Chait BT, MacKinnon R (2002) X-ray structure of a ClC chloride channel at 3.0A reveals the molecular basis of anion selectivity. Nature 415:287–294. https://doi.org/10.1038/415287a

    Article  CAS  PubMed  Google Scholar 

  46. Dutzler R, Campbell EB, MacKinnon R (2003) Gating the selectivity filter in ClC chloride channels. Science 300:108–112. https://doi.org/10.1126/science.1082708

  47. Eguchi H, Tsujino A, Kaibara M, Hayashi H, Shirabe S, Taniyama K, Eguchi K (2006) Acetazolamide acts directly on the human skeletal muscle chloride channel. Muscle Nerve 34:292–297

    CAS  PubMed  Google Scholar 

  48. Estévez R, Schroeder BC, Accardi A, Jentsch TJ, Pusch M (2003) Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1. Neuron 38:47–59

    PubMed  Google Scholar 

  49. Fahlke C, Knittle T, Gurnett C, Campbell K, George A Jr (1997) Subunit stoichiometry of human muscle chloride channels. J Gen Physiol 109(1):93–104. https://doi.org/10.1085/jgp.109.1.93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fahlke C, Yu HT, Beck CL, Rhodes TH, George AL Jr (1997) Poreforming segments in voltage-gated chloride channels. Nature 390:529–532

    CAS  PubMed  Google Scholar 

  51. Feng L, Campbell EB, Hsiung Y, MacKinnon R (2010) Structure of a eukaryotic CLC transporter defines an intermediate state in the transport cycle. Science 330:635–641. https://doi.org/10.1126/science.1195230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Fialho D, Schorge S, Pucovska U, Davies NP, Labrum R, Haworth A, Stanley E, Sud R, Wakeling W, Davis MB, Kullmann DM, Hanna MG (2007) Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions. Brain 130(Pt 12):3265–3274

    CAS  PubMed  Google Scholar 

  53. Fournier E, Tabti N (2019) Clinical electrophysiology of muscle diseases and episodic muscle disorders. Handb Clin Neurol 161:269–280. https://doi.org/10.1016/B978-0-444-64142-7.00053-9

    Article  PubMed  Google Scholar 

  54. Fraser JA, Huang CL, Pedersen TH (2011) Relationships between resting conductances, excitability, and t-system ionic homeostasis in skeletal muscle. J Gen Physiol 138:95–116

    PubMed  PubMed Central  Google Scholar 

  55. Furby A, Vicart S, Camdessanché JP, Fournier E, Chabrier S, Lagrue E, Paricio C, Blondy P, Touraine R, Sternberg D, Fontaine B (2014) Heterozygous CLCN1 mutations can modulate phenotype in sodium channel myotonia. Neuromuscul Disord 24(11):953–959. https://doi.org/10.1016/j.nmd.2014.06.439

    Article  CAS  PubMed  Google Scholar 

  56. George AL Jr, Crackower MA, Abdalla JA, Hudson AJ, Ebers GC (1993) Molecular basis of Thomsen’s disease (autosomal dominant myotonia congenita). Nat Genet 3:305–310. https://doi.org/10.1038/ng0493-305

    Article  CAS  PubMed  Google Scholar 

  57. Ginanneschi F, Mignarri A, Lucchiari S, Ulzi G, Comi GP, Rossi A, Dotti MT (2017) Neuromuscular excitability changes produced by sustained voluntary contraction and response to mexiletine in myotonia congenita. Neurophysiol Clin 47(3):247–252. https://doi.org/10.1016/j.neucli.2017.01.003

    Article  PubMed  Google Scholar 

  58. Goblet C, Whalen RG (1995) Modifications of gene expression in myotonic murine skeletal muscle are associated with abnormal expression of myogenic regulatory factors. Dev Biol 170:262–273

    CAS  PubMed  Google Scholar 

  59. Griggs RC, Moxley RT III, Riggs JE, Engel WK (1978) Effects of acetazolamide on myotonia. Ann Neurol 3:531–537

    CAS  PubMed  Google Scholar 

  60. Gutmann L, Phillips LH 2nd (1991) Myotonia Congenita. Semin Neurol 11(3):244–248. https://doi.org/10.1055/s-2008-1041228

    Article  CAS  PubMed  Google Scholar 

  61. Hao M, Akrami K, Wei K, De Diego C, Che N, Ku JH et al (2008) Muscleblind-like 2 (Mbnl2)-deficient mice as a model for myotonic dystrophy. Dev Dyn 237:403–410

    CAS  PubMed  Google Scholar 

  62. Hsiao KM, Huang RY, Tang PH, Lin MJ (2010) Functional study of CLC-1 mutants expressed in Xenopus oocytes reveals that a C-terminal region Thr891-Ser892-Thr893 is responsible for the effects of protein kinase C activator. Cell Physiol Biochem 25:687–694

    CAS  PubMed  Google Scholar 

  63. Imbrici P, Altamura C, Camerino GM, Mangiatordi GF, Conte E, Maggi L, Brugnoni R, Musaraj K, Caloiero R, Alberga D, Marsano RM, Ricci G, Siciliano G, Nicolotti O, Mora M, Bernasconi P, Desaphy JF, Mantegazza R, Camerino DC (2016) Multidisciplinary study of a new ClC-1 mutation causing myotonia congenita: a paradigm to understand and treat ion channelopathies. FASEB J 30(10):3285–3295

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Imbrici P, Altamura C, Pessia M, Mantegazza R, Desaphy JF, Camerino DC (2015) ClC-1 chloride channels: state-of-the-art research and future challenges. Front Cell Neurosci 9:156. https://doi.org/10.3389/fncel.2015.00156 eCollection 2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Imbrici P, Gualandi F, D'Adamo MC, Masieri MT, Cudia P, De Grandis D, Mannucci R, Nicoletti I, Tucker SJ, Ferlini A, Pessia M (2008) A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1. Neuroscience 157(3):577–587. https://doi.org/10.1016/j.neuroscience.2008.09.022

    Article  CAS  PubMed  Google Scholar 

  66. Imbrici P, Liantonio A, Camerino GM, De Bellis M, Camerino C, Mele A, Giustino A, Pierno S, De Luca A, Tricarico D, Desaphy JF, Conte D (2016) Therapeutic approaches to genetic ion channelopathies and perspectives in drug discovery. Front Pharmacol 7:121. https://doi.org/10.3389/fphar.2016.00121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Imbrici P, Liantonio A, Gradogna A, Pusch M, Camerino DC (2014) Targeting kidney CLC-K channels: pharmacological profile in a human cell line versus Xenopus oocytes. Biochim Biophys Acta 1838(10):2484–2491. https://doi.org/10.1016/j.bbamem.2014.05.017

    Article  CAS  PubMed  Google Scholar 

  68. Imbrici P, Maggi L, Mangiatordi GF, Dinardo MM, Altamura C, Brugnoni R, Alberga D, Pinter GL, Ricci G, Siciliano G, Micheli R, Annicchiarico G, Lattanzi G, Nicolotti O, Morandi L, Bernasconi P, Desaphy JF, Mantegazza R, Camerino DC (2015) ClC-1 mutations in myotonia congenita patients: insights into molecular gating mechanisms and genotype-phenotype correlation. J Physiol 593(18):4181–4199. https://doi.org/10.1113/JP270358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Jentsch TJ, Steinmeyer K, Schwarz G (1990) Primary structure of Torpedo marmorata chloride channel isolated by expression cloning in Xenopus oocytes. Nature 348:510–514

    CAS  PubMed  Google Scholar 

  70. Jentsch TJ, Pusch M (2018) CLC Chloride Channels and Transporters: Structure, Function, Physiology, and Disease. Physiol Rev 98(3):1493–1590

    CAS  PubMed  Google Scholar 

  71. Kato H, Kokunai Y, Dalle C, Kubota T, Madokoro Y, Yuasa H, Uchida Y, Ikeda T, Mochizuki H, Nicole S, Fontaine B, Takahashi MP, Mitake S (2016) A case of non-dystrophic myotonia with concomitant mutations in the SCN4A and CLCN1 genes. J Neurol Sci 369:254–258. https://doi.org/10.1016/j.jns.2016.08.030

    Article  CAS  PubMed  Google Scholar 

  72. Koch MC, Steinmeyer K, Lorenz C, Ricker K, Wolf F, Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ (1992) The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 257:797–800

    CAS  PubMed  Google Scholar 

  73. Koo T, Lu-Nguyen NB, Malerba A, Kim E, Kim D, Cappellari O, Cho HY, Dickson G, Popplewell L, Kim JS (2018) Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9. Mol Ther 26(6):1529–1538. https://doi.org/10.1016/j.ymthe.2018.03.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Lamb GD, Murphy RM, Stephenson DG (2011) On the localization of ClC-1 in skeletal muscle fibers. J Gen Physiol 137:327–329

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee TT, Zhang XD, Chuang CC, Chen JJ, Chen YA, Chen SC, Chen TY, Tang CY (2013) Myotonia congenita mutation enhances the degradation of human CLC-1 chloride channels. PLoS One 8(2):e55930. https://doi.org/10.1371/journal.pone.0055930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Liantonio A, Accardi A, Carbonara G, Fracchiolla G, Loiodice F, Tortorella P, Traverso S, Guida P, Pierno S, de Luca A, Camerino DC, Pusch M (2002) Molecular requisites for drug binding to muscle CLC-1 and renal CLC-K channel revealed by the use of phenoxy-alkyl derivatives of 2-(p-chlorophenoxy)propionic acid. Mol Pharmacol 62:265–271

    CAS  PubMed  Google Scholar 

  77. Liantonio A, Giannuzzi V, Picollo A, Babini E, Pusch M, Conte Camerino D (2007) Niflumic acid inhibits chloride conductance of rat skeletal muscle by directly inhibiting the CLC-1 channel and by increasing intracellular calcium. Br J Pharmacol 150:235–247

    CAS  PubMed  Google Scholar 

  78. Lo Monaco M, D'Amico A, Luigetti M, Desaphy J-F, Modoni A (2015) Effect of mexiletine on transitory depression of compound motor action potential in recessive myotonia congenita. Clin Neurophysiol 126:399–403

    PubMed  Google Scholar 

  79. Logigian EL, Martens WB, Moxley RT IV, McDermott MP, Dilek N, Wiegner AW et al (2010) Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Neurology 74:1441–1448. https://doi.org/10.1212/WNL.0b013e3181dc1a3a

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lueck JD, Lungu C, Mankodi A, Osborne RJ, Welle SL, Dirksen RT, Thornton CA (2007) Chloride channelopathy in myotonic dystrophy resulting from loss of posttranscriptional regulation for CLCN1. Am J Physiol Cell Physiol 292:C1291–C1297

    CAS  PubMed  Google Scholar 

  81. Lueck JD, Rossi AE, Thornton CA, Campbell KP, Dirksen RT (2010) Sarcolemmal-restricted localization of functional ClC-1 channels in mouse skeletal muscle. J Gen Physiol 136:597–613

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Ma L, Rychkov GY, Bykova EA, Zheng J, Bretag AH (2011) Movement of hClC-1 C-termini during common gating and limits on their cytoplasmic location. Biochem J 436:415–428

    CAS  PubMed  Google Scholar 

  83. Maffioletti SM, Sarcar S, Henderson ABH, Mannhardt I, Pinton L, Moyle LA, Steele-Stallard H, Cappellari O, Wells KE, Ferrari G, Mitchell JS, Tyzack GE, Kotiadis VN, Khedr M, Ragazzi M, Wang W, Duchen MR, Patani R, Zammit PS, Wells DJ, Eschenhagen T, Tedesco FS (2018) Three-dimensional human iPSC-derived artificial skeletal muscles model muscular dystrophies and enable multilineage tissue engineering. Cell Rep 23(3):899–908

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Maggi L, Ravaglia S, Farinato A, Brugnoni R, Altamura C, Imbrici P, Camerino DC, Padovani A, Mantegazza R, Bernasconi P, Desaphy JF, Filosto M (2017) Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia. Neurogenetics 18(4):219–225. https://doi.org/10.1007/s10048-017-0525-5

    Article  CAS  PubMed  Google Scholar 

  85. Manta A, Stouth DW, Xhuti D, Chi L, Rebalka IA, Kalmar JM, Hawke TJ, Ljubicic V (2019) Chronic exercise mitigates disease mechanisms and improves muscle function in myotonic dystrophy type 1 mice. J Physiol 597(5):1361–1381. https://doi.org/10.1113/JP277123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Markhorst JM, Stunnenberg BC, Ginjaar IB, Drost G, Erasmus CE, Sie LT (2014) Clinical experience with long-term acetazolamide treatment in children with nondystrophic myotonias: a three-case report. Pediatr Neurol 51:537–541

    PubMed  Google Scholar 

  87. Matthews E, Fialho D, Tan SV, Venance SL, Cannon SC, Sternberg D, Fontaine B, Amato AA, Barohn RJ, Griggs RC, Hanna MG, CINCH Investigators (2010) The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment. Brain 133:9–22

    CAS  PubMed  Google Scholar 

  88. Mazón MJ, Barros F, De la Peña P, Quesada JF, Escudero A, Cobo AM et al (2012) Screening for mutations in Spanish families with myotonia. Functional analysis of novel mutations in CLCN1 gene. Neuromuscul Disord 22:231–243

    PubMed  Google Scholar 

  89. Menegon A, Pitassi S, Mazzocchi N, Redaelli L, Rizzetto R, Rolland JF, Poli C, Imberti M, Lanati A, Grohovaz F (2017) A new electro-optical approach for conductance measurement: an assay for the study of drugs acting on ligand-gated ion channels. Sci Rep 7:44843

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Meola G, Cardani R (2015) Myotonic dystrophies: an update on clinical aspects, genetic, pathology, and molecular pathomechanisms. Biochim Biophys Acta 1852(4):594–606. https://doi.org/10.1016/j.bbadis.2014.05.019

    Article  CAS  PubMed  Google Scholar 

  91. Miller C, White MM (1984) Dimeric structure of single chloride channels from Torpedo electroplax. Proc Natl Acad Sci U S A 81:2772–2775

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Miranda DR, Wong M, Romer SH, McKee C, Garza-Vasquez G, Medina AC, Bahn V, Steele AD, Talmadge RJ, Voss AA (2017) Progressive Cl- channel defects reveal disrupted skeletal muscle maturation in R6/2 Huntington’s mice. J Gen Physiol 149(1):55–74. https://doi.org/10.1085/jgp.201611603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Modoni A, D’Amico A, Dallapiccola B, Mereu ML, Merlini L, Pagliarani S, Pisaneschi E, Silvestri G, Torrente I, Valente EM, Lo Monaco M (2011) Low-rate repetitive nerve stimulation protocol in an Italian cohort of patients affected by recessive myotonia congenita. J Clin Neurophysiol 28:39–44

    PubMed  Google Scholar 

  94. Montagnese F, Stahl K, Wenninger S, Schoser B (2020) A role for cannabinoids in the treatment of myotonia? Report of compassionate use in a small cohort of patients. J Neurol 267(2):415–421. https://doi.org/10.1007/s00415-019-09593-6

    Article  CAS  PubMed  Google Scholar 

  95. Morales F, Pusch M (2020) An up-to-date overview of the complexity of genotype-phenotype relationships in myotonic channelopathies. Front Neurol 10:1404. https://doi.org/10.3389/fneur.2019.01404

    Article  PubMed  PubMed Central  Google Scholar 

  96. Negishi Y, Endo-Takahashi Y, Ishiura S (2018) Exon skipping by ultrasound-enhanced delivery of morpholino with bubble liposomes for myotonic dystrophy model mice. Methods Mol Biol 1828:481–487. https://doi.org/10.1007/978-1-4939-8651-4_30

    Article  CAS  PubMed  Google Scholar 

  97. Nielsen OB, de Paoli F, Overgaard K (2001) Protective effects of lactic acid on force production in rat skeletal muscle. J Physiol 536:161–166

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Nielsen OB, de Paoli FV, Riisager A, Pedersen TH (2017) chloride channels take center stage in acute regulation of excitability in skeletal muscle: implications for fatigue. Physiology (Bethesda) 32(6):425–434. https://doi.org/10.1152/physiol.00006.2015

    Article  CAS  Google Scholar 

  99. Papponen H, Nissinen M, Kaisto T, Myllylä VV, Myllylä R, Metsikkö K (2008) F413C and A531V but not R894X myotonia congenita mutations cause defective endoplasmic reticulum export of the muscle-specific chloride channel CLC-1. Muscle Nerve 37:317–325

    CAS  PubMed  Google Scholar 

  100. Papponen H, Kaisto T, Myllylä VV, Myllylä R, Metsikkö K (2005) Regulated sarcolemmal localization of the muscle-specific ClC-1 chloride channel. Exp Neurol 191:163–173

    CAS  PubMed  Google Scholar 

  101. Park E, MacKinnon R (2018) Structure of the CLC-1 chloride channel from Homo sapiens. Elife 7:e36629. https://doi.org/10.7554/eLife.36629

    Article  PubMed  PubMed Central  Google Scholar 

  102. Pauly MG, Tunc S, Bäumer T, Gillessen-Kaesbach G, Münchau A (2019) “Twitching” and stiffness in POLG1 mutation carriers: red flag or red herring? Mov Disord Clin Pract 7(1):91–93. https://doi.org/10.1002/mdc3.12860

    Article  PubMed  Google Scholar 

  103. Peddareddygari LR, Grewal AS, Grewal RP (2016) Focal seizures in a patient with myotonic disorder type 2 co-segregating with a chloride voltage-gated channel 1 gene mutation: a case report. J Med Case Rep 10:167. https://doi.org/10.1186/s13256-016-0958-8

    Article  PubMed  PubMed Central  Google Scholar 

  104. Pedersen TH, de Paoli F, Nielsen OB (2005) Increased excitability of acidified skeletal muscle: role of chloride conductance. J Gen Physiol 125:237–246

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Pedersen TH, de Paoli FV, Flatman JA, Nielsen OB (2009a) Regulation of ClC-1 and KATP channels in action potential-firing fast-twitch muscle fibers. J Gen Physiol 134:309–322

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Pedersen TH, Macdonald WA, de Paoli FV, Gurung IS, Nielsen OB (2009b) Comparison of regulated passive membrane conductance in action potential-firing fast- and slow-twitch muscle. J Gen Physiol 134:323–337

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Pedersen TH, Riisager A, de Paoli FV, Chen TY, Nielsen OB (2016) Role of physiological ClC-1 Cl- ion channel regulation for the excitability and function of working skeletal muscle. J Gen Physiol 147(4):291–308. https://doi.org/10.1085/jgp.201611582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Peng YJ, Huang JJ, Wu HH, Hsieh HY, Wu CY, Chen SC, Chen TY, Tang CY (2016) Regulation of CLC-1 chloride channel biosynthesis by FKBP8 and Hsp90β. Sci Rep 6:32444. https://doi.org/10.1038/srep32444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Peng YJ, Lee YC, Fu SJ, Chien YC, Liao YF, Chen TY, Jeng CJ, Tang CY (2018) FKBP8 enhances protein stability of the CLC-1 chloride channel at the plasma membrane. Int J Mol Sci 19(12):E3783. https://doi.org/10.3390/ijms19123783

    Article  CAS  PubMed  Google Scholar 

  110. Pierno S, Camerino GM, Cippone V, Rolland J-F, Desaphy J-F, De Luca A et al (2009) Statins and fenofibrate affect skeletal muscle chloride conductance in rats by differently impairing ClC-1 channel regulation and expression. Br J Pharmacol 156:1206–1215

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Pierno S, De Luca A, Beck CL, George AL Jr, Conte Camerino D (1999) Aging-associated down-regulation of ClC-1 expression in skeletal muscle: phenotypic-independent relation to the decrease of chloride conductance. FEBS Lett 449(1):12–16

    CAS  PubMed  Google Scholar 

  112. Pierno S, De Luca A, Camerino C, Huxtable RJ, Camerino DC (1998) Chronic administration of taurine to aged rats improves the electrical and contractile properties of skeletal muscle fibers. J Pharmacol Exp Ther 286:1183–1190

    CAS  PubMed  Google Scholar 

  113. Pierno S, De Luca A, Desaphy J-F, Fraysse B, Liantonio A, Didonna MP et al (2003) Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin-specific receptor. Br J Pharmacol 139:575–584

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Pierno S, Desaphy J-F, Liantonio A, De Bellis M, Bianco G, De Luca A et al (2002) Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse. Brain 125:1510–1521

    PubMed  Google Scholar 

  115. Pierno S, Desaphy J-F, Liantonio A, De Luca A, Zarrilli A, Mastrofrancesco L et al (2007) Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance. J Physiol 584:983–995

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Pierno S, Tricarico D, Liantonio A, Mele A, Digennaro C, Rolland J-F et al (2014) An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function. Age (Dordr) 36:73–88

    CAS  Google Scholar 

  117. Portaro S, Altamura C, Licata N, Camerino GM, Imbrici P, Musumeci O, Rodolico C, Conte Camerino D, Toscano A, Desaphy JF (2015) Clinical, molecular, and functional characterization of CLCN1 mutations in three families with recessive myotonia congenita. NeuroMolecular Med 17(3):285–296. https://doi.org/10.1007/s12017-015-8356-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Harish P, Malerba A, Lu-Nguyen N, Forrest L, Cappellari O, Roth F, Trollet C, Popplewell L, Dickson G (2019) Inhibition of myostatin improves muscle atrophy in oculopharyngeal muscular dystrophy (OPMD). J Cachexia Sarcopenia Muscle 10(5):1016–1026. https://doi.org/10.1002/jcsm.12438

    Article  PubMed  PubMed Central  Google Scholar 

  119. Pusch M, Accardi A, Liantonio A, Guida P, Traverso S, Camerino DC, Conti F (2002) Mechanisms of block of muscle type CLC chloride channels. Mol Membr Biol 19(4):285–292

    CAS  PubMed  Google Scholar 

  120. Pusch M, Liantonio A, Bertorello L, Accardi A, De Luca A, Pierno S, Tortorella V, Camerino DC (2000) Pharmacological characterization of chloride channels belonging to the ClC family by the use of chiral clofibric acid derivatives. Mol Pharmacol 58(3):498–507

    CAS  PubMed  Google Scholar 

  121. Pusch M, Steinmeyer K, Jentsch TJ (1994) Low single channel conductance of the major skeletal muscle chloride channel, ClC-1. Biophys J 66:149–152

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Pusch M, Steinmeyer K, Koch MC, Jentsch TJ (1995) Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel. Neuron 15(6):1455–1463

    CAS  PubMed  Google Scholar 

  123. Raheem O, Penttilä S, Suominen T, Kaakinen M, Burge J, Haworth A, Sud R, Schorge S, Haapasalo H, Sandell S, Metsikkö K, Hanna M, Udd B (2012) New immunohistochemical method for improved myotonia and chloride channel mutation diagnostics. Neurology 79(22):2194–2200. https://doi.org/10.1212/WNL.0b013e31827595e2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Riisager A, de Paoli FV, Yu WP, Pedersen TH, Chen TY, Nielsen OB (2016) Protein kinase C-dependent regulation of ClC-1 channels in active human muscle and its effect on fast and slow gating. J Physiol 594(12):3391–3406. https://doi.org/10.1113/JP271556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Rosenbohm A, Rüdel R, Fahlke C (1999) Regulation of the human skeletal muscle chloride channel hClC-1 by protein kinase C. J Physiol 514:677–685

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Rychkov GY, Pusch M, Astill DS, Roberts ML, Jentsch TJ, Bretag AH (1996) Concentration and pH dependence of skeletal muscle chloride channel ClC-1. J Physiol 497:423–435

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Salviati G, Biasia E, Betto R, Danieli Betto D (1986) Fast to slow transition induced by experimental myotonia in rat EDL muscle. Pflugers Arch 406:266–272

    CAS  PubMed  Google Scholar 

  128. Sanarica F, Mantuano P, Conte E, Cozzoli A, Capogrosso RF, Giustino A, Cutrignelli A, Cappellari O, Rolland JF, De Bellis M, Denora N, Camerino GM, De Luca A (2019) Proof-of-concept validation of the mechanism of action of Src tyrosine kinase inhibitors in dystrophic mdx mouse muscle: in vivo and in vitro studies. Pharmacol Res 145:104260. https://doi.org/10.1016/j.phrs.2019.104260

    Article  CAS  PubMed  Google Scholar 

  129. Saviane C, Conti F, Pusch M (1999) The muscle chloride channel ClC-1 has a double-barreled appearance that is differentially affected in dominant and recessive myotonia. J Gen Physiol 113:457–468

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Skov M, De Paoli FV, Lausten J, Nielsen OB, Pedersen TH (2015) Extracellular magnesium and calcium reduce myotonia in isolated ClC-1 chloride channel-inhibited human muscle. Muscle Nerve 51:65–71

    CAS  PubMed  Google Scholar 

  131. Statland JM, Bundy BN, Wang Y, Rayan DR, Trivedi JR, Sansone VA, Salajegheh MK, Venance SL, Ciafaloni E, Matthews E, Meola G, Herbelin L, Griggs RC, Barohn RJ, Hanna MG, Consortium for Clinical Investigation of Neurologic Channelopathies (2012) Mexiletine for symptoms and signs of myotonia in nondystrophic myotonia: a randomized controlled trial. JAMA 308:1357–1365

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Steinmeyer K, Klocke R, Ortland C, Gronemeier M, Jockusch H, Grunder S et al (1991) Inactivation of muscle chloride channel by transposon insertion in myotonic mice. Nature 354:304–308

    CAS  PubMed  Google Scholar 

  133. Steinmeyer K, Ortland C, Jentsch TJ (1991) Primary structure and functional expression of a developmentally regulated skeletal muscle chloride channel. Nature 354:301–304

    CAS  PubMed  Google Scholar 

  134. Stunnenberg BC, Raaphorst J, Groenewoud HM, Statland JM, Griggs RC, Woertman W, Stegeman DF, Timmermans J, Trivedi J, Matthews E, Saris CGJ, Schouwenberg BJ, Drost G, van Engelen BGM, van der Wilt GJ (2018) Effect of mexiletine on muscle stiffness in patients with nondystrophic myotonia evaluated using aggregated N-of-1 trials. JAMA 320(22):2344–2353. https://doi.org/10.1001/jama.2018.18020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Suetterlin K, Männikkö R, Hanna MG (2014) Muscle channelopathies: recent advances in genetics, pathophysiology and therapy. Curr Opin Neurol 27(5):583–590. https://doi.org/10.1097/WCO.0000000000000127

    Article  CAS  PubMed  Google Scholar 

  136. Suetterlin KJ, Bugiardini E, Kaski JP, Morrow JM, Matthews E, Hanna MG, Fialho D (2015) long-term safety and efficacy of mexiletine for patients with skeletal muscle channelopathies. JAMA Neurol 72(12):1531–1533. https://doi.org/10.1001/jamaneurol.2015.2338

    Article  PubMed  Google Scholar 

  137. Thor MG, Vivekanandam V, Sampedro-Castañeda M, Tan SV, Suetterlin K, Sud R, Durran S, Schorge S, Kullmann DM, Hanna MG, Matthews E, Männikkö R (2019) Myotonia in a patient with a mutation in an S4 arginine residue associated with hypokalaemic periodic paralysis and a concomitant synonymous CLCN1 mutation. Sci Rep 9(1):17560. https://doi.org/10.1038/s41598-019-54041-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Tricarico D, Barbieri M, Camerino DC (2000) Acetazolamide opens the muscular KCa2+ channel: a novel mechanism of action that may explain the therapeutic effect of the drug in hypokalemic periodic paralysis. Ann Neurol 4:304–312

    Google Scholar 

  139. Tricarico D, Conte Camerino D, Govoni S, Bryant SH (1991) Modulation of rat skeletal muscle chloride channels by activators and inhibitors of protein kinase C. Pflugers Arch 418:500–503

    CAS  PubMed  Google Scholar 

  140. Trivedi JR, Cannon SC, Griggs RC (2014) Nondystrophic myotonia: challenges and future directions. Exp Neurol 253:28–30

    PubMed  Google Scholar 

  141. Tsujino A, Kaibara M, Hayashi H, Eguchi H, Nakayama S, Sato K, Fukuda T, Tateishi Y, Shirabe S, Taniyama K, Kawakami A (2011) A CLCN1 mutation in dominant myotonia congenita impairs the increment of chloride conductance during repetitive depolarization. Neurosci Lett 494:155–160

    CAS  PubMed  Google Scholar 

  142. Ugarte G, Cappellari O, Perani L, Pistocchi A, Cossu G (2012) Noggin recruits mesoderm progenitors from the dorsal aorta to a skeletal myogenic fate. Dev Biol 365(1):91–100. https://doi.org/10.1016/j.ydbio.2012.02.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Ulzi G, Lecchi M, Sansone V, Redaelli E, Corti E, Saccomanno D, Pagliarani S, Corti S, Magri F, Raimondi M, D’Angelo G, Modoni A, Bresolin N, Meola G, Wanke E, Comi GP, Lucchiari S (2012) Myotonia congenita: novel mutations in CLCN1 gene and functional characterizations in Italian patients. J Neurol Sci 318:65–71

    CAS  PubMed  Google Scholar 

  144. Ursu SF, Alekov A, Mao NH, Jurkat-Rott K (2012) ClC1 chloride channel in myotonic dystrophy type 2 and ClC1 splicing in vitro. Acta Myol 31:144–153

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Vindas-Smith R, Fiore M, Vásquez M, Cuenca P, Del Valle G, Lagostena L et al (2016) Identification and functional characterization of CLCN1 mutations found in nondystrophic myotonia patients. Hum Mutat 37(1):74–83. https://doi.org/10.1002/humu.22916

    Article  CAS  PubMed  Google Scholar 

  146. Wacker SJ, Jurkowski W, Simmons KJ, Fishwick CW, Johnson AP, Madge D, Lindahl E, Rolland JF, de Groot BL (2012) Identification of selective inhibitors of the potassium channel Kv1.1-1.2((3)) by high-throughput virtual screening and automated patch clamp. Chem Med Chem 7(10):1775–1783

    CAS  PubMed  Google Scholar 

  147. Wang K, Preisler SS, Zhang L, Cui Y, Missel JW, Grønberg C, Gotfryd K, Lindahl E, Andersson M, Calloe K, Egea PF, Klaerke DA, Pusch M, Pedersen PA, Zhou ZH, Gourdon P (2019) Structure of the human ClC-1 chloride channel. PLoS Biol 17(4):e3000218. https://doi.org/10.1371/journal.pbio.3000218

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Waters CW, Varuzhanyan G, Talmadge RJ, Voss AA (2013) Huntington disease skeletal muscle is hyperexcitable owing to chloride and potassium channel dysfunction. Proc Natl Acad Sci U S A 110:9160–9165

    CAS  PubMed  PubMed Central  Google Scholar 

  149. Weinberger S, Wojciechowski D, Sternberg D, Lehmann-Horn F, Jurkat-Rott K, Becher T, Begemann B, Fahlke C, Fischer M (2012) Disease-causing mutations C277R and C277Y modify gating of human ClC-1 chloride channels in myotonia congenita. J Physiol 590:3449–3464

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Wheeler TM, Lueck JD, Swanson MS, Dirksen RT, Thornton CA (2007) Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy. J Clin Invest 117:3952–3957

    CAS  PubMed  PubMed Central  Google Scholar 

  151. White MM, Miller C (1979) A voltage-gated anion channel from the electric organ of Torpedo californica. J Biol Chem 254(20):10161–10166

    CAS  PubMed  Google Scholar 

  152. Wu FF, Ryan A, Devaney J, Warnstedt M, Korade-Mirnics Z, Poser B, Escriva MJ, Pegoraro E, Yee AS, Felice KJ, Giuliani MJ, Mayer RF, Mongini T, Palmucci L, Marino M, Rüdel R, Hoffman EP, Fahlke C (2002) Novel CLCN1 mutations with unique clinical and electrophysiological consequences. Brain 125:2392–2407

    PubMed  Google Scholar 

  153. Zegarra-Moran O, Galietta LJ (2017) CFTR pharmacology. Cell Mol Life Sci 74(1):117–128. https://doi.org/10.1007/s00018-016-2392-x

    Article  CAS  PubMed  Google Scholar 

  154. Zhang XD, Tseng PY, Chen TY (2008) ATP inhibition of CLC-1 is controlled by oxidation and reduction. J Gen Physiol 132:421–428

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by Fondi Ateneo 2015-16 to P.I.

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences and Human Oncology, School of Medicine, University of Bari “Aldo Moro”, Bari, Italy

    Concetta Altamura & Jean-Francois Desaphy

  2. Department of Pharmacy–Drug Sciences, University of Bari “Aldo Moro”, Bari, Italy

    Diana Conte, Annamaria De Luca & Paola Imbrici

Authors
  1. Concetta Altamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jean-Francois Desaphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diana Conte
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Annamaria De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paola Imbrici
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paola Imbrici.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the special issue on Channelopathies: from mutation to diseases in Pflügers Archiv—European Journal of Physiology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Altamura, C., Desaphy, JF., Conte, D. et al. Skeletal muscle ClC-1 chloride channels in health and diseases. Pflugers Arch - Eur J Physiol 472, 961–975 (2020). https://doi.org/10.1007/s00424-020-02376-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-020-02376-3

Keywords

Search

Navigation