Critical Developmental Windows of Voltage-Gated Cation Channel Expression in Psychiatric Disorders

2021 ◽  
Vol 90 (6) ◽  
pp. e31-e32
Author(s):  
Noura Al-Juffali
Keyword(s):  
Psychiatric Disorders ◽  
Cation Channel ◽  
Voltage Gated ◽  
Channel Expression ◽  
Developmental Windows

scholarly journals Developmental profile of psychiatric risk associated with voltage-gated cation channel activity

2020 ◽  
Author(s):  
Nicholas E Clifton ◽  
Leonardo Collado-Torres ◽  
Emily E Burke ◽  
Antonio F Pardiñas ◽  
Janet C Harwood ◽  
...  
Keyword(s):  
Bipolar Disorder ◽  
Psychiatric Disorders ◽  
Association Studies ◽  
Early Adulthood ◽  
Biological Pathways ◽  
Cation Channel ◽  
Genome Wide Association Studies ◽  
Channel Activity ◽  
Voltage Gated ◽  
The Relationship

AbstractBackgroundRecent breakthroughs in psychiatric genetics have implicated biological pathways onto which genetic risk for psychiatric disorders converges. However, these studies do not reveal the developmental time point(s) at which these pathways are relevant.MethodsWe aimed to determine the relationship between psychiatric risk and developmental gene expression relating to discrete biological pathways. We used post-mortem RNA sequencing data (BrainSeq and BrainSpan) from brain tissue at multiple pre- and post-natal timepoints and summary statistics from recent genome-wide association studies of schizophrenia, bipolar disorder and major depressive disorder. We prioritised gene sets for overall enrichment of association with each disorder, and then tested the relationship between the association of each of their constituent genes with their relative expression at each developmental stage.ResultsWe observed relationships between the expression of genes involved in voltage-gated cation channel activity during Early Midfetal, Adolescence and Early Adulthood timepoints and association with schizophrenia and bipolar disorder, such that genes more strongly associated with these disorders had relatively low expression during Early Midfetal development and higher expression during Adolescence and Early Adulthood. The relationship with schizophrenia was strongest for the subset of genes related to calcium channel activity, whilst for bipolar disorder the relationship was distributed between calcium and potassium channel activity genes.ConclusionsOur results indicate periods during development when biological pathways related to the activity of calcium and potassium channels may be most vulnerable to the effects of genetic variants conferring risk to psychiatric disorders. Furthermore, they indicate key time points and potential targets for disorder-specific therapeutic interventions.

scholarly journals Voltage-gated calcium channel blockers for psychiatric disorders: genomic reappraisal

2019 ◽  
Vol 216 (5) ◽  
pp. 250-253 ◽  
Author(s):  
Paul J. Harrison ◽  
Elizabeth M. Tunbridge ◽  
Annette C. Dolphin ◽  
Jeremy Hall
Keyword(s):  
Calcium Channels ◽  
Calcium Channel ◽  
Psychiatric Disorders ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Risk Genes ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Voltage Gated Calcium Channel ◽  
Second Use

SummaryWe reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. Third, research shows there is an opportunity for brain-selective CCBs, which are better suited to psychiatric indications.

scholarly journals An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids

FEBS Letters ◽  
2015 ◽  
Vol 589 (5) ◽  
pp. 598-607 ◽  
Author(s):  
Joanna S. Amey ◽  
Andrias O. O'Reilly ◽  
Mark J. Burton ◽  
Alin M. Puinean ◽  
Ian R. Mellor ◽  
...  
Keyword(s):  
Cation Channel ◽  
Voltage Gated

Abstract 17384: Cardiac-Specific Overexpression of Human Mutant Desmoplakin in Mice Disrupts Cardiac Voltage-Gated Sodium Channel Expression

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Subat Turdi ◽  
Jeffrey A Towbin
Keyword(s):  
Sodium Channel ◽  
Fatty Infiltration ◽  
Electrical Coupling ◽  
Cx43 Expression ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Intercalated Discs ◽  
Channel Expression ◽  
Life Threatening ◽  
And Function

Introduction: Arrhythmogenic cardiomyopathy (AC) is characterized by bi-ventricular dilation, fibro-fatty infiltration and life-threatening arrhythmias. Disruptions in cardiac voltage-gated sodium channel (Nav1.5) expression and function are known to cause arrhythmias. We have demonstrated that cardiac-specific overexpression of human mutant desmoplakin (DSP, Tg-R2834H) in mice leads to AC. However, whether mutant DSP expression in the heart affects the Nav1.5 distribution and function are unknown Hypothesis: Here, we tested whether Nav1.5 localization and expression are altered in the R2834H-Tg mouse hearts. Methods: Primary cardiomyocytes and frozen myocardial sections from non-transgenic (NTg), wild-type DSP (Tg-DSP) and Tg-R2834H mice were used for immunofluorescence studies to assess subcellular localization of DSP, desmin, Nav1.5, Cx43, plakoglobin and β-catenin. Western blot and qPCR were used for quantitative analysis. Results: Double staining of cardiomyocytes from NTg mice with DSP and Nav1.5 revealed that Nav1.5 was colocalized with DSP at the intercalated discs (IDs). In contrast, Tg-R2834H cardiomyocytes exhibited marked increase of mutant DSP expression at the IDs concomitant with a reduction in Nav1.5 immunoreactive signals. Tg-R2834H cardiomyocytes also revealed an aberration of DSP and desmin colocalizations at the IDs. There were not obvious differences in Cx43 expression between the genotypes, although the redistribution of Cx43 from the IDs to the sarcolemma was evident in Tg-R2834H cardiomyocytes. qPCR results correlated with reduced Nav1.5 mRNA expression in the Tg-R2834H mouse hearts. Conclusions: Defective DSP protein expression in the heart disrupts Nav1.5 localization and expression, implying an interaction between DSP and Nav1.5 to orchestrate normal mechanical and electrical coupling. Further electrophysiology studies to assess whole-cell Na + currents in these cardiomyocytes will provide insight into DSP and Nav1.5 interaction.

Elevated voltage gated Cl− channel expression enhances fast paired-pulse inhibition in the dentate gyrus of seizure sensitive gerbil

2005 ◽  
Vol 51 (1) ◽  
pp. 45-53 ◽  
Author(s):  
Duk-Soo Kim ◽  
Ki-Yeon Yoo ◽  
In-Koo Hwang ◽  
Ju-Young Jung ◽  
Moo Ho Won ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Paired Pulse ◽  
Voltage Gated ◽  
Cl Channel ◽  
Channel Expression

Cyclic nucleotide-gated cation channel expression in embryonic chick brain

1999 ◽  
Vol 66 (1-2) ◽  
pp. 175-178 ◽  
Author(s):  
Leslie C. Timpe ◽  
Kun Lin Jin ◽  
Luis Puelles ◽  
John L.R. Rubenstein
Keyword(s):  
Cyclic Nucleotide ◽  
Cation Channel ◽  
Embryonic Chick ◽  
Chick Brain ◽  
Channel Expression

scholarly journals Role of K+ channel expression in polyamine-dependent intestinal epithelial cell migration

2000 ◽  
Vol 278 (2) ◽  
pp. C303-C314 ◽  
Author(s):  
Jian-Ying Wang ◽  
Jian Wang ◽  
Vera A. Golovina ◽  
Li Li ◽  
Oleksandr Platoshyn ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Driving Force ◽  
Intestinal Epithelial Cell ◽  
Delayed Rectifier ◽  
Intestinal Epithelial ◽  
Voltage Gated ◽  
Epithelial Cell Migration ◽  
Channel Expression ◽  
Exogenous Spermidine

Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K+ channels (Kv) controls membrane potential ( E m) that regulates cytoplasmic free Ca2+ concentration ([Ca2+]cyt) by governing the driving force for Ca2+ influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K+ channel gene expression, E m, and [Ca2+]cyt in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, α-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca2+ channels, the depolarized E m in DFMO-treated cells decreased [Ca2+]cyt as a result of reduced driving force for Ca2+ influx through capacitative Ca2+ entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E m, and [Ca2+]cyt but also restored cell migration to normal. Removal of extracellular Ca2+ or blockade of Kv channels (by 4-aminopyridine, 1–5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca2+]cyt by increasing the driving force (the electrochemical gradient) for Ca2+ influx and thus stimulates cell migration.

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