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Review

Molecular biology of channelopathies: impact on diagnosis and treatment

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Pages 519-539 | Published online: 10 Jan 2014

References

  • Creutzfeldt OD, Abbott BC, Fowler WM, Pearson CM. Muscle membrane potentials in episodic adynamia. Electroencephalogr Clin. Neurophysiol 15,508–519 (1963).
  • Lehmann-Horn F, Rudel R, Dengler R, Lorkovic H, Haass A, Ricker K. Membrane defects in paramyotonia congenita with and without myotonia in a warm environment. Muscle Nerve 4,396–406 (1981).
  • Ptacek LJ, George AL, Griggs RC et al Identification of a mutation in the genecausing hyperkalemic periodic paralysis. Ce1167, 1021–1027 (1991).
  • Rojas CV, Wang JZ, Schwartz LS, Hoffman EP, Powell BR, Brown RII. A Met-to-Valmutation in the skeletal muscle Na+ channel CL-subunit in hyperkalaemic periodic paralysis. Nature 354,387–389 (1991).
  • Strafstrom CE, Schwindt PC, Flatman JA, Crill WE. Properties of subthreshold response and action potential recorded in layer V neurons from cat sensorimotor cortex in vitro. .1. Neurophysiol 52, 244–263 (1984).
  • Mantegazza M, Franceschetti S, Avanzini G. Anemone toxin (ATXII) induced increase in persistent sodium current: effects on the firing properties of rat neocortical pyramidal neurones. I Physiol 507,105–116 (1998).
  • •Provides the first direct evidence that a selective enhancement of the persistent fraction of Na+ current induces paroxysmal discharges in neocortical pyramidal neurons.
  • Bargmann CI. Neurobiology of the Caenorhabditis elegansgenome. Science 282, 2028–2033 (1998).
  • Rogawski MA. KCNQ2/IKCNQ3 channels and the molecular pathogenesis of epilepsy: implications for therapy. TINS 23,393–398 (2000).
  • Singh NA, Charlier C, Stauffer D et al. A novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns. Nature Genet. 18, 25–29 (1998).
  • Charlier C, Singh NA, Ryan SG et al A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nature Genet. 18,53–55 (1998).
  • Wang HS, Pan Z, Shi W et al KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. Science 282,1890–1893 (1998).
  • •Coexpression of two different K+ subunits demonstrates that they both contribute to the M-type channel. This result provides an unitary pathogenetic interpretation for benign neonatal familial convulsions that may be associated to mutations of two different genes coding respectively for KCNQ2 and KCNQ3 K+subunits.
  • Eunson LH, Rea R, Zuberi SM et al. genetic and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability. Ann. Neural 48,647–656 (2000).
  • ••Describes three new point mutations inthe voltage-gated potassium channel gene KCNAI leading to phenotypes different from typical EAl: partial epilepsy and myokymia, myokymia alone, remarkably drug-resistant EA1 and suggest that the degree and nature of the potassium channel dysfunction may be relevant to the reported new phenotypic observations.
  • Zhang JF, Randall AD, Ellinor PT et al. Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts on mammalian CNS neurons. Neuropharmacology 32, 1075–1088 (1993).
  • Vergnes M, Marescaux C, Micheletti G et al Spontaneous paroxysmal electroclinical patterns in rat: a model of generalized nonconvulsive epilepsy. Neurosci. Lett. 33,97–101 (1982).
  • Coenen AML, Drinkenburg WHIM, Inoue M, Van Luijtelaar ELJM. Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats. Epilepsy Res. 12,75–87 (1992).
  • Burgess DL, Noebels JL. Voltage- dependent calcium channel mutations in neurological disease. Ann. NY Acad. 868, 199–212 (1999).
  • Avanzini G, de Curtis M, Panzica F, Spreafico R. Intrinsic properties of nucleus reticularis thalami neurones of the rat studies in vitro. Physiol 416,111–122 (1989).
  • Avanzini G, Vergnes M, Spreafico R, Marescaux C. Calcium-dependent regulation of genetically determined spike and waves by the reticular thalamic nucleus of rats. Epilepsia 34,1–7 (1993).
  • Avanzini G, de Curtis M, Pape HC, Spreafico R. Intrinsic properties of reticular thalamic neurons relevant to genetically determined spike-wave generation. In: Advances in Neurology Volume 79. Jasperi. Basic Mechanisms of the Epilepsies. Third Edition. Delgado-Escueta AV, Wilson WA, Olsen RVV, Porter RJ (Eds). Lippincott Williams & Wilkins, PA, USA, 297–309 (1999).
  • Tsakiridou E, Bertollini L, de Curtis M, Avanzini G, Pape HC. Selective increase in T-type calcium conductance of reticular thalamic neurons in a rat model of absence epilepsy. Neurosci. 15,3110–3117 (1995).
  • Odermatt A, Barton K, Khanna VK et al The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease. Hum. Genet. 106(5), 482–491 (2000).
  • McCarthy TV, Quane IKA, Lynch PJ. Ryanodine receptor mutations in malignant hyperthermia and central core disease. Hum. Mutat. 5(5), 410–417 (2000).
  • Cooper JR, Bloom FE, Roth RII. The Biochemical Basis of Neuropharmacology Oxford University Press, Oxford, UK, 88–119 and 190–219 (1991).
  • •• Describes the biochemical basis of acetylcholine metabolism and the structure of cholinergic receptors.
  • Zhou L, Chillag KL, Nigro MA. Hyperekplexia: a treatable neurogenetic disease. Brain Dev. 669–674 (2002).
  • Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Frog. Neurobial 54, 581–618 (1998).
  • Najm IM, Ying Z, Babb T, Mohamed A et al Epileptogenicity correlated with increased Nmethyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia. Epilepsia 41,971–976 (2000).
  • Tinuper P, Cerullo A, Cirignotta F, Cortelli P, Lugaresi E, Montagna P. Nocturnal paroxysmal dystonia with short-lasting attacks: three case with evidence for an epileptic frontal lobe origin of seizures. Epilepsia 31,549–556 (1990).
  • Scheffer IE, Bhatia IKP, Lopes-Cendes I et al. Autosomal dominant frontal epilepsy misdiagnosed as sleep disorder. Lancet 343, 515–517 (1994).
  • Steinlein 0, Mulley JC, Propping P et al A missense mutation in the neuronal nicotinic acetylcholine receptor a4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Natum Genet. 11, 201–203 (1995).
  • •Reports the fist evidence of a channelopathy accounting for the pathogenesis of a genetically determined epileptic syndrome.
  • De Fusco M, Becchetti A, Patrignani A et al The nicotinic receptor p2 subunits is mutant innocturnal frontal lobe epilepsy. Nature Genet. 26,275–276 (2000).
  • Biervert C, Schroeder BC, Kubisch C et al. A potassium channel mutation in neonatal human epilepsy. Science 279,403–406 (1998).
  • Heron SE, Crossland KM, Andermann E et al. Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 360,851–882 (2002)
  • Scheffer IE, Berkovic SE Generalized epilepsies with febrile seizures plus — a genetic disorder with heterogeneous clinical phenotypes. Brain 120,479–490 (1997).
  • Wallace RII, Wang DW, Singh R et al Febrile seizures and generalized epilepsy associated with a mutation in the Nat channel 01 subunit gene SCN1B. Nature Genet. 19,366–370 (1998).
  • Escayg A, MacDonald T, Meisler MET et al. Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Natum Genet. 24,343–345 (2000).
  • Lossin C, Wang DW, Rhodes TH, Vanoye CG, George AL Jr. Molecular basis of an inherited epilepsy. Neuron 34(6), 877–84 (2002).
  • ••Uses the heterologous expression ofSCN1A the authors provided the evidence that SCN1A mutations alter channel inactivation and lead to a significantly enhancement of the persistent fraction of Na+ current accounting for the generation of epileptic discharges that are responsible for generalized epilepsy with febrile seizures plus.
  • Baulac S, Huberfeld G, Gourfinkel-An I et al. First genetic evidence of GABAA receptor dysfunction in epilepsy: a mutation in the y2-subunit gene. Nature Genet. 28,46–48 (2001).
  • Wallace RII, Marini C, Petrou S et al Mutant GABA(A) receptor y2-subunit in childhood absence epilepsy and febrile seizures. Natum Genet. 28(1), 49–52 (2001).
  • Claes L, Del Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 1327–1332 (2001).
  • ••Results highlighted the possibility thatnoninherited, de novo occurring mutations of genes coding for ion channels can be responsible for sporadic epilepsies.
  • Fujiwara T, Sugawara T, Mazaki-Miyazaki E et al Mutations of sodium channel a subunit Type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic—clonic seizures. Brain 126,531–546 (2003).
  • Kim D, Song I, Keum S, Lee T et al. Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking a(1G) T-type Ca2+ channels. Neuron 31,35–45 (2001).
  • Jouvenceau A, Eunson LH, Spauschus A et al Human epilepsy associated with dysfunction of the brain P/Q-type calcium channel. Lancet 358,801–807 (2001).
  • Cossette P, Liu L, Brisebois K et al Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nature Genet. 31,184–189 (2002).
  • Haug K, Warnstedt M, Alekov AK et al Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nature Genet. 33,527–532 (2003).
  • •The reported mutation is suggested to represented a common predisposing factor for different types of idiopathic epilepsies that are currently considered distinct.
  • Lipicky RJ, Gilbert DL, Stillman IM. Diphenylhydantoin inhibition of sodium conductance in squid giant axon. Proc. Natl Acad. Li. USA 69,1758–1760 (1972).
  • Willow M, Gonoi T, Catterall WA. Voltage clamp analysis of the inhibitory actions of diphenylhydantoin and carbamazepine on voltage-sensitive sodium channels in neuroblastoma cells. Mal Pharmacol 27, 549–558 (1985).
  • Zona C, Avoli M. Effects induced by the antiepileptic drug valproic acid upon the ionic currents recorded in rat neocortical neurons in cell colture. Exp. Brain Res. 81, 313–317 (1990).
  • Cheung H, Kamp D, Harris E. An in vitro investigation of the action of lamotrigine on neuronal voltage activated sodium channels. Epilepsy Res. 13, 107–112 (1992).
  • Zona C, Ciotti MT, Avoli M. Topiramate attenuates voltage gated sodium currents in rat cerebellar granule cells. Neurosci. Lett. 231,123–126 (1997).
  • Schechter PJ, Trainer Y, Jung MJ, Boehlen Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of gamma-acetylenic GABA and gamma-vinyl GABA, two irreversible GABA-T inhibitors. Eur j Pharmacol 45, 319–328 (1977).
  • Braestrup C, Nielsen EB, Sonnewald U et al. (R)-N-(4,4-bis[3-methyl-2-thienylibut-3-en-1-yOnipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier. J. Neurochem. 54(2), 639–647 (1990).
  • Chao TT, Alzheimer C. Effects of phenytoin on the persistent Na+ current of mammalian CNS neurones. .Ai,umReport6, 1778–1780 (1995).
  • Taverna S, Sancini G, Mantegazza M, Franceschetti S, Avanzini G. Inhibition of transient and persistent Na+ current fractions by the new anticonvulsant topiramate. j Pharmacol Exp. Ther. 288, 960–968 (1999).
  • Lukyanetz EA, Shkryl VM, Kostyuk PG. Selective blockade of N-type calcium channels by levitiracetam. Epilepsia 43, 9–18 (2002)
  • Wickenden AD, Yu W, Zou A, Jegla T, Wagoner PK. Retigabine, a novel anticonvulsant, enhances activation of KCNQ2/Q3 potassium channels. Mal Pharmacol 58,591–600 (2000).
  • Picard F, Bertrand S, Steinlein OK, Bertrand D. Mutated nicotinic receptors responsible for autosomal dominant nocturnal frontal lobe epilepsy are more sensitive to carbamazepine. Epilepsia 40, 1198–1209 (1999).
  • Van Dyke DH, Griggs RC, Murphy MJ, Goldstein MN. Hereditary myokymia and periodic ataxia. J. Neural Sci. 25,109–118 (1975).
  • •Describes for the first time a family with episodic ataxia in which affected individuals have persistent myokymia and evaluated the effect of caloric vestibular stimulation on ataxic attacks and myokymia.
  • Browne DL, Gancher ST, Nutt JG et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNAL Natum Genet. 8,136–140 (1994).
  • Zuberi SM, Eunson LH, Spauschus A et al A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia Type 1 and sometimes with partial epilepsy. Brain 122 (Pt 5), 817–825 (1999).
  • •Reports a family with EA1 harbouring a novel mutation in the human voltage-gated potassium channel (Kv1.1) gene in which there was evidence of an over-representation of epilepsy in family members and they suggest that the epilepsy in EA1 may be caused by the dysfunctional potassium channel.
  • Liguori R, Avoni P, Baruzzi A, Di Stasi V, Montagna P Familial continuous motor unit activity and epilepsy. Muscle Nerve. 24(5), 630–633 (2001).
  • Eulenberg A. Ueber eine familiare, durch 6 generationen verfolgbare Form congenitaler Paramyotonie. Neurologisches Centmlblatt. 12,265–272 (1886).
  • Ptacek LJ, Trimmer JS, Agnew WS, Roberts JW, Petajan JH, Leppert M. Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus. Am. j Hum. Genet. 49, 851–854 (1991).
  • ••Reports for the first time a linkagebetween pararnyotonia congenita and skeletal muscle sodium-channel gene and suggested that pararnyotonia congenita and hyperkalemic periodic paralysis are allelic disorders.
  • Ptacek LJ, Tawil R, Griggs RC et al. Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita and hyperkalemic periodic paralysis. Neumlogy 44,1500–1503 (1994).
  • ••Summarizes the sodium channel mutationanalysis in different families with hyperkalemic periodic paralysis and pararnyotonia congenita.
  • Ricker K, Moxley RT III, Heine R, Lehmann-Horn E Myotonia fluctuans: a third type of muscle sodium channel disease. Awl?. Neural 51,1095–1102 (1994).
  • •Identifies the mutation in the gene for the skeletal muscle sodium channel leading to myotonia fluctuans and described the clinical features of this disease.
  • Cannon SC. Spectrum of sodium channel disturbances in the nondystrophic myotonias and periodic paralyses. IGclney hit 57,772-779 (2000). Focuses on sodium channels defects, underlying myotonias and periodic paralysis at molecular and functional levels.
  • Thomsen J. Tonische Kraempfe in willkuerlich beweglichen Muskeln in Folge von ererbter psychischer disposition: ataxia muscularis? Arch. Bychiat. Nervenkr 6, 702–718 (1876).
  • Becker PE. Zur Genetik der Myotonien. In: Progressive Muskel*tivphie, 4otonie, 11/1Yasthenie. Kuhn E (Ed.). Springer-Verlag, Berlin, Germany, 247–255 (1966).
  • Abdalla JA, Casley WL, Cousin HK et al Linkage of Thomsen disease to the T-cell-receptor 13 (TCRB) locus on chromosome 7q35. Ainj Hum. Genet. 51,579-584 (1992).
  • Otto M, Zoll B, Lehmann-Horn F, Grzeschik KH, Jentsch TJ. The skeletal muscle chloride channel in dominant and recessive human myotonia. Science 257, 797–800 (1992).
  • Meyer-Kleine C, Steinmeyer K, Ricker K, Jentsch TJ, Koch MC. Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia. Am. J. Hum. Genet. 57,1325-1334 (1995).
  • Mailander V, Heine R, Deymeer F, Lehmann-Horn E Novel muscle chloride channel mutations and their effects on heterozygous carriers. Am. J. Hum. Genet. 58,317–324 (1996).
  • Lehmann-Horn F, Mailander V, Heine R, George AL. Myotonia levior is a chloride channel disorder. Hum. Mal Genet. 4, 1397–402 (1995).
  • Sun C, Tranebjaerg L, Torbergsen T, Holmgren G, Van Ghelue M. Spectrum of CLCN1 mutations in patients with myotonia congenita in Northern Scandinavia. Eur. J. Hum. Genet. 9, 903–909 (2001).
  • Pusch M. Myotonia caused by mutations in the muscle chloride channel gene CLCN1. Hum. Mutat. 19,423-434 (2002).
  • Plassart E, Elbaz A, Santos JV et al. Genetic heterogeneity in hypokalemic periodic paralysis (hypoPP). Hum. Genet. 94, 551–556 (1994).
  • ••Describes the genetic heterogeneity inhypokalemic periodic paralysis.
  • Fontaine B, Vale-Santos J, Jurkat-Rott K et al Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families. Nature Genet. 6,267–272 (1994).
  • Bulman DE, Scoggan IKA, van Oene MD et al A novel sodium channel mutation in a family with hypokalemic periodic paralysis. Neurology1932-1936 (1999).
  • Abbott GW, Butler MET, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SAN. MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell 104, 217–231 (2001).
  • Jurkat-Rott K, Lehmann-Horn F, Elbaz A et al A calcium channel mutation causing hypokalemic periodic paralysis. Hum. Mal Genet. 3,1415–1419 (1994).
  • ••Describes a new mutation in the gene forthe skeletal muscle dihydropyridine receptor associated with a form of hypokalemic periodic paralysis
  • Jurkat-Rott K, Mitrovic N, Hang C et al Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis Type 2 by enhanced inactivation and reduced current. Proc. Natl Acad. Sci. 97, 9549–9554 (2000).
  • •Identifies a missense mutation in the gene for MiRP2 (KCNE3) which segregate with periodic paralysis and suggested that MiRP2 operates with a classical potassium channel subunit to govern skeletal muscle function and pathophysiology.
  • Dias Da Silva MR, Cerutti JM, Arnaldi LAT, Maciel RMB. A mutation in the KCNE3 potassium channel gene is associated with susceptibility to thyrotoxic hypokalemic periodic paralysis. J. Clin. Enclocr Metab. 87,4881-4884 (2002).
  • Ptacek LJ, Tawil R, Griggs RC et al. Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. C1117 (77), 863–868 (1994).
  • ••Describes a new mutation in the gene forthe skeletal muscle dihydropyridine receptor associated with a form of hypokalemic periodic paralysis.
  • Plaster NM, Tawil R, Tristani-Firouzi M et al. Mutations in KiR2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome. Cell 105,511–519 (2001).
  • Lopes CM, Zhang H, Rohacs T, Jin T, Yang, J, Logothetis DE. Alterations in conserved Kir channel-PIP(2) interactions underlie channelopathies. Neuron 34, 933–944 (2002).
  • •Shows that several naturally occurring mutants decrease interactions between Kir channels and phosphatidylinositol 4,5-bisphosphate, leading to Andersen's and Bartter's syndromes.
  • Lehmann-Horn F, Jurkat-Rott K, Rudel R. Periodic paralysis: understanding channelopathies. Curr Neural Neurosci. Rep. 2,61–69 (2002).
  • ••The relationship between periodicparalysis phenotypes and type of functional defects are described.
  • Andersen ED, Krasilnikoff PA, Overvad, H. Intermittent muscular weakness, extrasystoles and multiple developmental anomalies: a new syndrome? Acta Paecliat. Scam 60,559–564 (1971).
  • Sansone V, Griggs RC, Meola G et al. Andersen's syndrome: a distinct periodic paralysis. Ann. Neural 42,305–312 (1997).
  • Tristani-Firouzi M, Jensen JL, Donaldson MR et al Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome).j Clin Invest 110, 381–388 (2002).
  • •Characterizes the functional consequences of three novel and seven previously described KCNJ2 mutations, leading to Andersen syndrome and correlated the findings with the clinical phenotype.
  • Andelfinger G, Tapper AR, Welch RC, Vanoye CG, George AL Jr, Benson DW. KCNJ2 mutation results in Andersen syndrome with sex-specific cardiac and skeletal muscle phenotypes. Am. J. Hum. Genet. 71,663-668 (2002).
  • Shy GM, Magee KR. A new congenital nonprogressive myopathy. Brain 79, 610–621 (1956).
  • Eng GD, Epstein BS, Engel WK, McKay DW, McKay R. Malignant hyperthermia and central core disease in a child with congenital dislocating hips: case presentation and review. Arch. Neural 35, 189–197 (1978).
  • Manzur AY, Sewry CA, Ziprin J, Dubowitz V, Muntoni E A severe clinical and pathological variant of central core disease with possible autosomal recessive inheritance. Neuromusc. Disord 8,467–473 (1998).
  • Ferreiro A, Monnier N, Romero NB et al. A recessive form of central core disease, transiently presenting as multiminicore disease, is associated with a homozygous mutation in the ryanodine receptor Type 1 gene. Ann. Neural. 51,750-759 (2002).
  • Jungbluth H, Muller CR, Halliger-Keller B et al Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores. Neurology 59, 284–287 (2002).
  • Quane IKA, Healy JMS, Keating KE et al Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia. Nature Genet. 5,51–55 (1993).
  • •Identifies two new mutations in the ryanodine receptor gene, related with central core disease and malignant hyperthermia and suggested a model to explain how a single mutation may result in two apparently distinct clinical phenotypes.
  • Lynch PJ, Tong J, Lehane M et al. A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca(2+) release channel function and severe central core disease. Proc. Nat. Acad. Sc]. 96, 4164–4169 (1999).
  • Brody IA. Muscle contracture induced by exercise: a syndrome attributable to decreased relaxing factor. N Engl. I Med. 281,187–192 (1969).
  • Karpati G, Charuk J, Carpenter S, Jablecki C, Holland P. Myopathy caused by a deficiency of Ca(2+)-adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease). Ann. Neural 20,38–49 (1986).
  • Odermatt A, Taschner PEM, Khanna VK et al. Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca(2+) ATPase, are associated with Brody disease. Nature Genet. 14,191–194 (1996).
  • •In this report Brody's disease is associated with the autosomal recessive inheritance of three ATP2A1 mutations in two families.
  • Odermatt A, Taschner PEM, Scherer S. W et al Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCAl: absence of structural mutations in five patients with Brody disease. Genomics 45,541–553 (1997).
  • Taylor DJ, Brosnan MJ, Arnold DL et al Ca(2+)-ATPase deficiency in a patient with exertional muscle pain syndrome. j Neural. Neurosurg. PTchiat. 51,1425-1433 (1988).
  • Lindstrom JM. Acetylcholine receptors and myasthenia. Muscle Nerve. 23,453–477 (2000).
  • ••The structure of acetylcholine receptorsand the immunological and genetic basis of my-asthenic disorders are described.
  • Tricarico D, Barbieri M, Camerino DC. 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. Neural 48(3), 304–312 (2000).
  • •Investigates the mechanism of action of acetazolamide in the K-deficient diet rat and demonstrated that the therapeutic effects of acetazolamide in the K-deficient diet rats can be mediated by activation of the KCa2+ channel. They suggested that a similar mechanism of action could explain the therapeutic effect of this drug in patients with hypokalemic periodic paralysis.
  • Kuzmenkin A, Muncan V, Jurkat-Rott K et al Enhanced inactivation and pH sensitivity of Na(+) channel mutations causing hypokalaemic periodic paralysis Type II. Brain 125 (Pt 4), 835–843 (2002).
  • •Expresses different mutations in the SCN4A gene, associated with hypokalaemic periodic paralysis phenotype, in a human cell line and studied them electrophysiologically.
  • Takahashi MP, Cannon SC. Mexiletine block of disease-associated mutations in S6 segments of the human skeletal muscle Na+ channel.J Physiol 537\(Pt 3), 701–714 (2001).
  • •Examines state-dependent modletine block for mutations involving the putative binding site of the adult skeletal muscle Na(+) channel (hSkIVI1), associated with myotonia or periodic paralysis.
  • Abicht A, Muller-Felber W, Fischer P et al Congenital myasthenic syndromes: clinical and genetic analysis of 18 patients. Eur. Med. Res. 2 (12), 515–522 (1997).
  • Dorian P. Mechanisms of action of class III agents and their clinical relevance. Review. Europace l(Suppl. C), C6—C9 (2000).
  • •Considers the antiarrhythmic agents Class ifi and their mode of action with the aim to provide a basis for rational drug choice when managing particular rhythm disturbances.
  • Junker J, Haverkamp W, Schulze-Bahr E, Eckardt L, Paulus W, Kiefer R. Amiodarone and acetazolamide for the treatment of genetically confirmed severe Andersen syndrome. Neurology59, 466 (2002).
  • Benders AAGM, Veerkamp JH, Oosterhof A et al. Ca(2+) homeostasis in Brody's disease: a study in skeletal muscle and cultured muscle cells and the effects of dantrolene and verapamil. j Gun. Invest. 94,741-748 (1994).
  • Dedkova EN, Wang YG, Blatter LA, Lipsius SL. Nitric oxide signalling by selective 13(2) -adrenoceptor stimulation prevents ACh-induced inhibition of (2)-stimulated Ca(2+) current in cat atrial myocytes. I Physiol 542,711–723 (2002).
  • Wang, Q, Shen J, Splawski I et al SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. c1180, 805–811 (1995).
  • Kambouris NG, Nuss HB, Johns DC, Marban E, Tomaselli G F, Balser J R. A revised view of cardiac sodium channel blockade in the long-QT syndrome. j din. Invest. 105,1133–1140 (2000).
  • ••Examines the effect of lidocaine on asingle-channel openings mutation of the cardiac sodium channel and showed that the drug does not block the open pore but it augments the propensity of the mutant channels to inactivate the channel.
  • Clancy CE, Rudy Y. Na + channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 105,1208–1213 (2002).
  • Makita N, Shirai N, Wang DW et al Cardiac No+ channel dysfunction in Brugada syndrome is aggravated by (1)-subunit. Circulation 101,54–60 (2000).
  • Wang Q, Curran ME, Splawski I et al Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nature Genet. 12, 17–23 (1996).
  • Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Ce1180, 795–803 (1995).
  • Abbott GW, Sesti F, Splawski I et al MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97 (2), 175–187 (1999).
  • Keller DI, Carrier L, Schwartz K. Genetics of familial cardiomyopathies and arrhythmias. Swiss Med. Week. 132, 401–407 (2002) .
  • •Describes the clinical and genetic features of the most important familial cardiomyopathies and arrhythmiail
  • Tiso N, Stephan DA, Nava A et al. Identification of mutations in the cardiac ryanodine receptor gene in families affected with arrhythmogenic right ventricular cardiomyopathy Type 2 (ARVD2). Hum. Malec. Genet. 10,189-194 (2001).
  • Wang W, Viswanathan PC, Balser JR, George AL Jr, Benson W Clinical, genetic and biophysical characterisation of SCN5A mutations associated with atrioventricular block. Circulation 105,341–346 (2002).
  • Priori SG, Napolitano C, Tiso N et al. Mutations in the cardiac ryanodine receptor gene (hRyR2) underlie catecholaminergic polymorphic ventricular tachycardia. Circulation 102, R49—R53, (2000).
  • Laitinen PJ, Brown KM, Piippo K et al Mutations of the cardiac ryanodine receptor (RyR2) gene in familial polymorphic ventricular tachycardia. Circulation 103,485–490 (2001).
  • Itoh T, Kikuchi K, Odagawa Y et al Correlation of genetic etiology with response to fi -adrene rgi c blockade among symptomatic patients with familial long-QT syndrome. Hum. Genet. 46 (1), 38–40 (2001).
  • Mbai M, Rajamani S, January CT The antimalarial drug halofantrine and its metabolite N-desbutylhalofantrine block HERG potassium channels. Canliovasc. Res. 55(4), 799–805 (2002).
  • Sesti F, Abbott GW, Wei J et al. A common polymorphism associated with antibiotic-induced cardiac arrhythmia. Proc. Natl. Acad. Sci. USA 97(19), 10613–10618 (2000).
  • Kyrmizakis DE, Chimona TS, Kanoupakis EM, Papadakis CE, Velegrakis GA, Helidonis ES. QT prolongation and torsades de pointes associated with concurrent use of cisapride and erythromycin. Am. j Otolaryngol 23(5), 303–307(2002).
  • Ptacek U. Channelopathies: ion channel disorders of muscle as a paradigm for paroxysmal disorders of the nervous system. Neuromusc Disord. 7,250–255 (1997).
  • •The concept of channelopathy and its potential value for understanding the pathogenesis of paroxysmal disorders are illustrated by the scientist who pioneered its foundation.
  • Lehmann-Horn F, Rudel R. Muscle nerve. Molecular pathophysiology of voltage-gated ion channels. Rev. Physiol Biochem. Pharmacol 128,195–268 (1996).
  • Lerche H, Jurkat-Rott K, Lehmann-Horn F. Ion channels and epilepsy. Am. j Med. Genet. 106,146–159 (2001).
  • Cannon SC. Ion-channel defects and aberrant excitability in myotonia and periodic paralysis. Trends Neurosci. 19, 3–10 (1996)
  • Cannon SC. An expanding view for the molecular basis of familial periodic paralysis. Neuromuscul Disoffl 12, 533–543 (2002).
  • Hille B. Ion Channels of Excitable Nkmbtanes. Thin] Edition. Sinaver Associates Inc. Publishers, MA, USA (2001).
  • Catterall WA. Structure and regulation of voltage-gated Ca2+ channels. Ann. Rev Cell Dev. Biol. 16,521-555 (2000).
  • Catterall WA. From ionic curents to molecular mechanisms: the structur and function of voltage-gated sodium channels. Neuron 26,1225 (2000).

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