Felix R (2000), Channelopathies: ion channel defects linked to ...

XB-ART-51549

J Med Genet 2000 Oct 01;3710:729-40.

Show Gene links Show Anatomy links

Channelopathies: ion channel defects linked to heritable clinical disorders.

Felix R .

???displayArticle.abstract???
Electrical signals are critical for the function of neurones, muscle cells, and cardiac myocytes. Proteins that regulate electrical signalling in these cells, including voltage gated ion channels, are logical sites where abnormality might lead to disease. Genetic and biophysical approaches are being used to show that several disorders result from mutations in voltage gated ion channels. Understanding gained from early studies on the pathogenesis of a group of muscle diseases that are similar in their episodic nature (periodic paralysis) showed that these disorders result from mutations in a gene encoding a voltage gated Na(+) channel. Their characterisation as channelopathies has served as a paradigm for other episodic disorders. For example, migraine headache and some forms of epilepsy have been shown to result from mutations in voltage gated Ca(2+) channel genes, while long QT syndrome is known to result from mutations in either K(+) or Na(+) channel genes. This article reviews progress made in the complementary fields of molecular genetics and cellular electrophysiology which has led to a better understanding of voltage gated ion channelopathies in humans and mice.

???displayArticle.pubmedLink??? 11015449
???displayArticle.pmcLink??? PMC1757150
???displayArticle.link??? J Med Genet

GO keywords: chloride channel activity [+]

???displayArticle.disOnts??? benign neonatal seizures [+]
???displayArticle.omims??? EPISODIC ATAXIA, TYPE 2; EA2 [+]
References [+] :

Abbott, MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. 1999, Pubmed, Xenbase

Abbott, MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. 1999, Pubmed , Xenbase
Adelman, Episodic ataxia results from voltage-dependent potassium channels with altered functions. 1995, Pubmed , Xenbase
Armstrong, Voltage-gated ion channels and electrical excitability. 1998, Pubmed
Arnoult, Control of the low voltage-activated calcium channel of mouse sperm by egg ZP3 and by membrane hyperpolarization during capacitation. 1999, Pubmed
Ball, The genetics of malignant hyperthermia. 1993, Pubmed
Bech-Hansen, Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. 1998, Pubmed
Bech-Hansen, Localization of a gene for incomplete X-linked congenital stationary night blindness to the interval between DXS6849 and DXS8023 in Xp11.23. 1998, Pubmed
Bendahhou, Characterization of a new sodium channel mutation at arginine 1448 associated with moderate Paramyotonia congenita in humans. 1999, Pubmed
Bennett, Molecular mechanism for an inherited cardiac arrhythmia. 1995, Pubmed , Xenbase
Biervert, A potassium channel mutation in neonatal human epilepsy. 1998, Pubmed , Xenbase
Black, Identification and cloning of putative human neuronal voltage-gated calcium channel gamma-2 and gamma-3 subunits: neurologic implications. 1999, Pubmed
Block, Structural evidence for direct interaction between the molecular components of the transverse tubule/sarcoplasmic reticulum junction in skeletal muscle. 1988, Pubmed
Browne, Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. 1994, Pubmed
Burgess, Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'. 1995, Pubmed
Burgess, Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. 1997, Pubmed
Burgess, Genetic localization of the Ca2+ channel gene CACNG2 near SCA10 on chromosome 22q13. 2000, Pubmed
Campbell, L-type calcium channels contribute to the tottering mouse dystonic episodes. 1999, Pubmed
Catterall, Structure and function of voltage-gated ion channels. 1995, Pubmed
Chen, Impaired cerebellar synapse maturation in waggler, a mutant mouse with a disrupted neuronal calcium channel gamma subunit. 1999, Pubmed
Cooper, Ion channel genes and human neurological disease: recent progress, prospects, and challenges. 1999, Pubmed
Deal, Molecular physiology of cardiac potassium channels. 1996, Pubmed
De Waard, Ca2+ channel regulation by a conserved beta subunit domain. 1994, Pubmed , Xenbase
Di Pasquale, Increased excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mutant mouse Stargazer. 1997, Pubmed
Dove, Whole-cell and single-channel analysis of P-type calcium currents in cerebellar Purkinje cells of leaner mutant mice. 1998, Pubmed
Dumaine, Multiple mechanisms of Na+ channel--linked long-QT syndrome. 1996, Pubmed , Xenbase
Dunlap, Exocytotic Ca2+ channels in mammalian central neurons. 1995, Pubmed
Ertel, Nomenclature of voltage-gated calcium channels. 2000, Pubmed
Escayg, Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. 2000, Pubmed , Xenbase
Featherstone, A defect in skeletal muscle sodium channel deactivation exacerbates hyperexcitability in human paramyotonia congenita. 1998, Pubmed
Fletcher, Absence epilepsy in tottering mutant mice is associated with calcium channel defects. 1996, Pubmed
Fontaine, Mapping of the hypokalaemic periodic paralysis (HypoPP) locus to chromosome 1q31-32 in three European families. 1994, Pubmed
Fontaine, Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene. 1990, Pubmed
Gao, Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2). 2000, Pubmed , Xenbase
García, The sodium channel Scn8a is the major contributor to the postnatal developmental increase of sodium current density in spinal motoneurons. 1998, Pubmed
Gurnett, Extracellular interaction of the voltage-dependent Ca2+ channel alpha2delta and alpha1 subunits. 1997, Pubmed
Haeseler, Voltage-dependent block of normal and mutant muscle sodium channels by 4-Chloro-m-Cresol. 1999, Pubmed
Harris, Neuromuscular transmission in the murine mutants "motor end-plate disease" and "jolting". 1986, Pubmed
Hayward, Defective slow inactivation of sodium channels contributes to familial periodic paralysis. 1999, Pubmed
Holz, Chromosomal localization of the myelin-associated oligodendrocytic basic protein and expression in the genetically linked neurological mouse mutants ducky and tippy. 1997, Pubmed
Iles, Localization of the gene encoding the alpha 2/delta-subunits of the L-type voltage-dependent calcium channel to chromosome 7q and analysis of the segregation of flanking markers in malignant hyperthermia susceptible families. 1994, Pubmed
Ishikawa, Japanese families with autosomal dominant pure cerebellar ataxia map to chromosome 19p13.1-p13.2 and are strongly associated with mild CAG expansions in the spinocerebellar ataxia type 6 gene in chromosome 19p13.1. 1997, Pubmed
Jodice, Episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6) due to CAG repeat expansion in the CACNA1A gene on chromosome 19p. 1997, Pubmed
Kohrman, A missense mutation in the sodium channel Scn8a is responsible for cerebellar ataxia in the mouse mutant jolting. 1996, Pubmed
Kohrman, Mutation detection in the med and medJ alleles of the sodium channel Scn8a. Unusual splicing due to a minor class AT-AC intron. 1996, Pubmed
Kraus, Familial hemiplegic migraine mutations change alpha1A Ca2+ channel kinetics. 1998, Pubmed , Xenbase
Lapie, Electrophysiological properties of the hypokalaemic periodic paralysis mutation (R528H) of the skeletal muscle alpha 1s subunit as expressed in mouse L cells. 1996, Pubmed
Lasater, Torsade des pointes--etiology and treatment. 1986, Pubmed
Letts, The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit. 1998, Pubmed
Letts, Genetic and physical maps of the stargazer locus on mouse chromosome 15. 1997, Pubmed
Lorenzon, Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner. 1998, Pubmed
Lory, Towards a unified nomenclature describing voltage-gated calcium channel genes. 1997, Pubmed
Lüthi, Periodicity of thalamic synchronized oscillations: the role of Ca2+-mediated upregulation of Ih. 1998, Pubmed
MacLennan, The role of the skeletal muscle ryanodine receptor gene in malignant hyperthermia. 1992, Pubmed
Matsuyama, Molecular features of the CAG repeats of spinocerebellar ataxia 6 (SCA6). 1997, Pubmed
McEnery, Altered expression and assembly of N-type calcium channel alpha1B and beta subunits in epileptic lethargic (lh/lh) mouse. 1998, Pubmed
Monnier, Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. 1997, Pubmed
Morrill, Effects of mutations causing hypokalaemic periodic paralysis on the skeletal muscle L-type Ca2+ channel expressed in Xenopus laevis oocytes. 1999, Pubmed , Xenbase
Navarro, Nonselective and G betagamma-insensitive weaver K+ channels. 1996, Pubmed
Neyroud, A novel mutation in the potassium channel gene KVLQT1 causes the Jervell and Lange-Nielsen cardioauditory syndrome. 1997, Pubmed
Ophoff, Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. 1996, Pubmed
Patil, A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation. 1995, Pubmed
Plassart-Schiess, Functional expression of the Ile693Thr Na+ channel mutation associated with paramyotonia congenita in a human cell line. 1998, Pubmed
Ptacek, Linkage of atypical myotonia congenita to a sodium channel locus. 1992, Pubmed
Ptácek, Dihydropyridine receptor mutations cause hypokalemic periodic paralysis. 1994, Pubmed
Ptácek, Identification of a mutation in the gene causing hyperkalemic periodic paralysis. 1991, Pubmed
Ptáĉek, Sodium channel mutations in acetazolamide-responsive myotonia congenita, paramyotonia congenita, and hyperkalemic periodic paralysis. 1994, Pubmed
Ricker, Myotonia fluctuans. A third type of muscle sodium channel disease. 1994, Pubmed
Robinson, A genome wide search for susceptibility loci in three European malignant hyperthermia pedigrees. 1997, Pubmed
Rojas, Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel. 1999, Pubmed , Xenbase
Sah, Effects of local anesthetics on Na+ channels containing the equine hyperkalemic periodic paralysis mutation. 1998, Pubmed , Xenbase
Sasaki, Neuropathological and molecular studies of spinocerebellar ataxia type 6 (SCA6). 1998, Pubmed
Schleithoff, Genomic structure and functional expression of a human alpha(2)/delta calcium channel subunit gene (CACNA2). 1999, Pubmed
Smart, Deletion of the K(V)1.1 potassium channel causes epilepsy in mice. 1998, Pubmed
Smith, The inward rectification mechanism of the HERG cardiac potassium channel. 1996, Pubmed
Southan, Patch-clamp recordings from cerebellar basket cell bodies and their presynaptic terminals reveal an asymmetric distribution of voltage-gated potassium channels. 1998, Pubmed
Splawski, Molecular basis of the long-QT syndrome associated with deafness. 1997, Pubmed
Splawski, Mutations in the hminK gene cause long QT syndrome and suppress IKs function. 1997, Pubmed , Xenbase
Steger, Drug-induced torsade des pointes: case report and implications for the critical care staff. 1986, Pubmed
Steinlein, Idiopathic epilepsies with a monogenic mode of inheritance. 1999, Pubmed
Strom, An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness. 1998, Pubmed
Sudbrak, Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the alpha 1, beta 1, and gamma subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect. 1993, Pubmed
Surmeier, The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells. 1996, Pubmed
Vetter, Inner ear defects induced by null mutation of the isk gene. 1996, Pubmed
Wakamori, Single tottering mutations responsible for the neuropathic phenotype of the P-type calcium channel. 1998, Pubmed
Wang, Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. 1996, Pubmed
Wang, Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. 1993, Pubmed , Xenbase
Wang, Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. 1996, Pubmed
Wang, SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. 1995, Pubmed
Wang, KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. 1998, Pubmed , Xenbase
Watanabe, Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability. 2000, Pubmed
Zhuchenko, Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha 1A-voltage-dependent calcium channel. 1997, Pubmed