Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization

Trosclair, Krystle; Si, Man; Watts, Megan N.; Gautier, Nicole; Voigt, Niels; Traylor, James; Bitay, Miklós; Baczkó, István; Dobrev, Dobromir; Hamilton, Katherine; Bhuiyan, Shenuarin; Dominic, Paari; Glasscock, Edward

doi:10.14814/phy2.14702

Cited by 8 publications

(5 citation statements)

References 32 publications

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“…It has been suggested that neuroinflammation plays a role in FIRES-associated epileptogenesis in animal models of infection (Galic et al, 2012;Riazi et al, 2010), as well as febrile and afebrile SE later developing epilepsy (Dubé et al, 2010). Neuroinflammation reduces seizure threshold rather than triggering seizures, thus FIRES shows a delayed onset (van Baalen et al, 2017).…”

Section: Seizuresmentioning

confidence: 99%

“…When a previously healthy child sustains severe refractory SE after a brief recovery from a short febrile disease, and infectious encephalitis is ruled out, then the condition can be suspected as febrile infection-related epilepsy syndrome (FIRES) (van Baalen et al, 2017). FIRES is a sporadic condition.…”

Section: Seizuresmentioning

confidence: 99%

“…The central nervous system (CNS) is composed of different kinds of glial cells including astrocytes, oligodendrocytes, ependymal cells, microglia, and Bergmann glia (Foresti et al, 2011 ; Patel et al, 2019 ). Glial cells may direct a feeding mechanism, signal transduction from blood to neurons, removal of synaptic glutamate, neuronal path finding, and the sequestration and redistribution of K + ion (Foresti et al, 2011 ; Trosclair et al, 2021 ). The K + long‐range spatial buffering conducted by glia is a parallel synchronizing and/or spreading mechanism during paroxysmal oscillations (Chung et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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The role of astrocytes in epileptic disorders

Hayatdavoudi

Hosseini

Hajali

et al. 2022

Physiological Reports

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Epilepsy affects about 1% of the population and approximately 30% of epileptic patients are resistant to current antiepileptic drugs. As a hallmark in epileptic tissue, many of the epileptic patients show changes in glia morphology and function. There are characteristic changes in different types of glia in different epilepsy models. Some of these changes such as astrogliosis are enough to provoke epileptic seizures. Astrogliosis is well known in mesial temporal lobe epilepsy (MTLE), the most common form of refractory epilepsy. A better understanding of astrocytes alterations could lead to novel and efficient pharmacological approaches for epilepsy. In this review, we present the alterations of astrocyte morphology and function and present some instances of targeting astrocytes in seizure and epilepsy.

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Section: Seizuresmentioning

confidence: 99%

Section: Seizuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The role of astrocytes in epileptic disorders

Hayatdavoudi

Hosseini

Hajali

et al. 2022

Physiological Reports

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“…(2016), 38 Glasscock et al (2015), 39 Trosclair et al (2020), 40 Trosclair et al (2021), 41 Glasscock et al (2019), 42 Frasier et al (2016). 43 AV, atrioventricular; CPVT, Catecholaminergic polymorphic ventricular tachycardia; VF, Ventricular fibrillation.…”

Section: Epilepsy and Arrhythmiasmentioning

confidence: 99%

The brain–heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention

Costagliola

Orsini

Coll

et al. 2021

Ann Clin Transl Neurol

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The influence of the central nervous system and autonomic system on cardiac activity is being intensively studied, as it contributes to the high rate of cardiologic comorbidities observed in people with epilepsy. Indeed, neuroanatomic connections between the brain and the heart provide links that allow cardiac arrhythmias to occur in response to brain activation, have been shown to produce arrhythmia both experimentally and clinically. Moreover, seizures may induce a variety of transient cardiac effects, which include changes in heart rate, heart rate variability, arrhythmias, asystole, and other ECG abnormalities, and can trigger the development of Takotsubo syndrome. People with epilepsy are at a higher risk of death than the general population, and sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Although the cause of SUDEP is still unknown, cardiac abnormalities during and between seizures could play a significant role in its pathogenesis, as highlighted by studies on animal models of SUDEP and registration of SUDEP events. Recently, genetic mutations in genes co-expressed in the heart and brain, which may result in epilepsy and cardiac comorbidity/increased risk for SUDEP, have been described. Recognition and a better understanding of brainheart interactions, together with new advances in sequencing techniques, may provide new insights into future novel therapies and help in the prevention of cardiac dysfunction and sudden death in epileptic individuals.

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“…The Kv channels also play a role in calcium signaling, cell proliferation, migration, differentiation, cell death and maintenance of cell volume ( Bachmann et al, 2020 ). Deficiency of Kv channels leads to neurological and metabolic disorders, cardiovascular and autoimmune diseases, cancer, and deafness ( Glasscock et al, 2010 ; Leitner et al, 2011 ; Anderson et al, 2019 ; Trosclair et al, 2021 ). Therapeutically, the Kv channel activators or blockers alter the action potential’s firing pattern ( Vyas et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic deletion of Kvβ2 (AKR6) causes loss of muscle function and increased inflammation in mice

et al. 2023

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The voltage-gated potassium channels (Kv) are complex ion channels with distinct roles in neurotransmission, electrical conductivity of the heart, and smooth and striated muscle functions. Previously, we demonstrated that deletion of Kvβ2 in mice results in decreased Pax7 protein levels, hindlimb muscles and body weights, and fiber type switching. In the present study, we tested the hypothesis that Kvβ2 regulates skeletal muscle function in mice. The young and old Kvβ2 knockout (KO) and wildtype (WT) mice were utilized to test the aging phenotype and skeletal muscle function. Consistent with our previous finding, we found a significant reduction in hindlimb skeletal muscles mass and body weight in young Kvβ2 KO mice, which was also significantly reduced in old Kvβ2 KO mice compared with age-matched WT mice. Forelimb grip strength, and the hindleg extensor digitorum longus (EDL) muscles force-frequency relations were significantly decreased in young and old Kvβ2 KO mice compared to age-matched WT mice. Analysis of transmission electron microscopy images of EDL muscles in young mice revealed a significant reduction in the sarcomere length for Kvβ2 KO vs. WT. Hematoxylin and eosin-stained tibialis anterior muscles cryosections displayed a significant decrease in the number of medium (2,000–4,000 µm2) and largest (>4,000 µm2) myofibers area in young Kvβ2 KO vs. WT mice. We also found a significant increase in fibrotic tissue area in young Kvβ2 KO mice compared with age-matched WT mice. Analysis of RNA Seq data of the gastrocnemius muscles (GAS) identified significant increase in genes involved in skeletal muscle development, proliferation and cell fate determination, atrophy, energy metabolism, muscle plasticity, inflammation, and a decrease in circadian core clock genes in young Kvβ2 KO vs. WT mice. Several genes were significantly upregulated (384 genes) and downregulated (40 genes) in young Kvβ2 KO mice compared to age-matched WT mice. Further, RT-qPCR analysis of the GAS muscles displayed a significant increase in pro-inflammatory marker Il6 expression in young Kvβ2 KO mice compared to age-matched WT mice. Overall, the present study shows that deletion of Kvβ2 leads to decreased muscles strength and increased inflammation.

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Kv1.1 potassium channel subunit deficiency alters ventricular arrhythmia susceptibility, contractility, and repolarization

Cited by 8 publications

References 32 publications

The role of astrocytes in epileptic disorders

The role of astrocytes in epileptic disorders

The brain–heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention

Genetic deletion of Kvβ2 (AKR6) causes loss of muscle function and increased inflammation in mice

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