Homozygous SCN1B variants causing early infantile epileptic encephalopathy 52 affect voltage‐gated sodium channel function

Epilepsia ◽  
2021 ◽  
Author(s):  
Marcello Scala ◽  
Stephanie Efthymiou ◽  
Tipu Sultan ◽  
Jolien De Waele ◽  
Marta Panciroli ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Epileptic Encephalopathy ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Function

scholarly journals The Sialic Acid Component of the β1Subunit Modulates Voltage-gated Sodium Channel Function

2004 ◽  
Vol 279 (43) ◽  
pp. 44303-44310 ◽  
Author(s):  
Daniel Johnson ◽  
Marty L. Montpetit ◽  
Patrick J. Stocker ◽  
Eric S. Bennett
Keyword(s):  
Sialic Acid ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Acid Component ◽  
Voltage Gated ◽  
Channel Function

scholarly journals Alternative splicing potentiates dysfunction of early-onset epileptic encephalopathy SCN2A variants

2020 ◽  
Vol 152 (3) ◽  
Author(s):  
Christopher H. Thompson ◽  
Roy Ben-Shalom ◽  
Kevin J. Bender ◽  
Alfred L. George
Keyword(s):  
Alternative Splicing ◽  
Sodium Channel ◽  
Early Onset ◽  
Neuronal Excitability ◽  
Epileptic Encephalopathy ◽  
Developmentally Regulated ◽  
Voltage Gated Sodium Channel ◽  
Splice Isoforms ◽  
Voltage Gated ◽  
Splice Isoform

Epileptic encephalopathies are severe forms of infantile-onset epilepsy often complicated by severe neurodevelopmental impairments. Some forms of early-onset epileptic encephalopathy (EOEE) have been associated with variants in SCN2A, which encodes the brain voltage-gated sodium channel NaV1.2. Many voltage-gated sodium channel genes, including SCN2A, undergo developmentally regulated mRNA splicing. The early onset of these disorders suggests that developmentally regulated alternative splicing of NaV1.2 may be an important consideration when elucidating the pathophysiological consequences of epilepsy-associated variants. We hypothesized that EOEE-associated NaV1.2 variants would exhibit greater dysfunction in a splice isoform that is prominently expressed during early development. We engineered five EOEE-associated NaV1.2 variants (T236S, E999K, S1336Y, T1623N, and R1882Q) into the adult and neonatal splice isoforms of NaV1.2 and performed whole-cell voltage clamp to elucidate their functional properties. All variants exhibited functional defects that could enhance neuronal excitability. Three of the five variants (T236S, E999K, and S1336Y) exhibited greater dysfunction in the neonatal isoform compared with those observed in the adult isoform. Computational modeling of a developing cortical pyramidal neuron indicated that T236S, E999K, S1336Y, and R1882Q showed hyperexcitability preferentially in immature neurons. These results suggest that both splice isoform and neuronal developmental stage influence how EOEE-associated NaV1.2 variants affect neuronal excitability.

scholarly journals Gastric hyperalgesia and changes in voltage gated sodium channel function in the rat

Gut ◽  
2002 ◽  
Vol 51 (Supplement 1) ◽  
pp. i15-i18 ◽  
Author(s):  
G F Gebhart ◽  
K Bielefeldt ◽  
N Ozaki
Keyword(s):  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Function

scholarly journals Thiazolidinediones Alter Lipid Bilayer Properties and Native Voltage-Gated Sodium Channel Function

2010 ◽  
Vol 98 (3) ◽  
pp. 480a
Author(s):  
Radda Rusinova ◽  
Karl F. Herold ◽  
Roger E. Koeppe ◽  
Hugh C. Hemmings ◽  
Olaf S. Andersen
Keyword(s):  
Sodium Channel ◽  
Lipid Bilayer ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Channel Function

The Voltage-Gated Sodium Channel Nav1.2 Contributes to Neurodegeneration in an Animal Model of Multiple Sclerosis

2016 ◽  
Vol 47 (S 01) ◽  
Author(s):  
W. Fazeli ◽  
B. Schattling ◽  
B. Engeland ◽  
M. Friese ◽  
D. Isbrand
Keyword(s):  
Multiple Sclerosis ◽  
Animal Model ◽  
Sodium Channel ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated
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