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Full-Text Articles in Neuroscience and Neurobiology
Myotonia Congenita, Christoph Lossin, Alfred George
Myotonia Congenita, Christoph Lossin, Alfred George
Christoph Lossin, Ph.D.
Myotonia is a symptom of many different acquired and genetic muscular conditions that impair the relaxation phase of muscular contraction. Myotonia congenital is a specific inherited disorder of muscle membrane hyperexcitability caused by reduced sarcolemmal chloride conductance due to mutations invCLCN1, the gene coding for the main skeletal muscle chloride channel ClC-1.The disorder may be transmitted as either an autosomal-dominant or recessive trait with close to 130 currently known mutations. Although this is a rare disorder, elucidation of the pathophysiology underlying myotonia congenital established the importance of sarcolemmal chloride conductance in the control of muscle excitability and demonstrated the first …
A Catalog Of Scn1a Variants, Christoph Lossin
A Catalog Of Scn1a Variants, Christoph Lossin
Christoph Lossin, Ph.D.
Over the past 10 years mutations in voltage-gated sodium channels (Navs) have become closely associated with inheritable forms of epilepsy. One isoform in particular, Nav1.1 (gene symbol SCN1A), appears to be a superculprit, registering with more than 330 mutations to date. The associated phenotypes range from benign febrile seizures to extremely serious conditions, such as Dravet’s syndrome (SMEI). Despite the wealth of information, mutational analyses are cumbersome, owing to inconsistencies among the Nav1.1 sequences to which different research groups refer. Splicing variability is the core problem: Nav1.1 co-exists in three isoforms, two of them lack 11 or 28 amino acids …
Single-Channel Properties Of Human Nav1.1 And Mechanism Of Channel Dysfunction In Scn1a-Associated Epilepsy, C. Vanoye, Christoph Lossin, T. H. Rhodes, Alfred L. George
Single-Channel Properties Of Human Nav1.1 And Mechanism Of Channel Dysfunction In Scn1a-Associated Epilepsy, C. Vanoye, Christoph Lossin, T. H. Rhodes, Alfred L. George
Christoph Lossin, Ph.D.
Mutations in genes encoding neuronal voltage-gated sodium channel subunits have been linked to inherited forms of epilepsy. The majority of mutations (>100) associated with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) occur in SCN1A encoding the NaV1.1 neuronal sodium channel alpha-subunit. Previous studies demonstrated functional heterogeneity among mutant SCN1A channels, revealing a complex relationship between clinical and biophysical phenotypes. To further understand the mechanisms responsible for mutant SCN1A behavior, we performed a comprehensive analysis of the single-channel properties of heterologously expressed recombinant WT-SCN1A channels. Based on these data, we then determined the …
Epilepsy-Associated Dysfunction In The Voltage-Gated Neuronal Sodium Channel Scn1a, Christoph Lossin, T. Rhodes, R. Desai, C. Vanoye, S. Caniciu, O. Devinsky, A. George
Epilepsy-Associated Dysfunction In The Voltage-Gated Neuronal Sodium Channel Scn1a, Christoph Lossin, T. Rhodes, R. Desai, C. Vanoye, S. Caniciu, O. Devinsky, A. George
Christoph Lossin, Ph.D.
Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel subunit (Nav1.1) are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density and …
Molecular Basis Of An Inherited Epilepsy, Christoph Lossin, T. H. Rhodes, C. Vanoye, D. Wang, Alfred L. George
Molecular Basis Of An Inherited Epilepsy, Christoph Lossin, T. H. Rhodes, C. Vanoye, D. Wang, Alfred L. George
Christoph Lossin, Ph.D.
Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha1 subunit (NaV1.1), are associated with at least two forms of epilepsy, generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI). We examined the functional properties of four GEFS+ alleles and one SMEI allele using whole-cell patch-clamp analysis of heterologously expressed recombinant human SCN1A. One previously reported GEFS+ mutation (I1656M) and an additional novel allele (R1657C), both affecting residues in a voltage-sensing S4 segment, exhibited a similar depolarizing shift in the voltage dependence of activation. Additionally, R1657C showed a 50% reduction in current density …