The Role of Calcium Channels in Epilepsy

Rajakulendran, Sanjeev; Hanna, Michael G.

doi:10.1101/cshperspect.a022723

Cited by 80 publications

(48 citation statements)

References 261 publications

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“…In survey of the data in literature to understand the effect of lovastatin in AS model, we noted a report that lovastatin may act as an L-type calcium channel blocker (Bergdahl et al 2003). The involvement of L-type calcium channel in epilepsy and the anticonvulsant effect of the antagonist have been reported (Nicita et al 2016; Rajakulendran and Hanna 2016). To test if antagonizing L-type calcium channels can suppress the long burst, we chose nimodipine, which is in clinical use for hypertension and in human epilepsy by the case report (Nicita et al 2016; Zamponi et al 2015).…”

Section: Resultsmentioning

confidence: 99%

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Chung

Bey

Towers

et al. 2018

Neurobiology of Disease

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Epilepsy is prevalent and often medically intractable in Angelman syndrome (AS). AS mouse model (Ube3am−/p+) shows reduced excitatory neurotransmission but lower seizure threshold. The neural mechanism linking the synaptic dysfunction to the seizure remains elusive. We show that the local circuits of Ube3am−/p+ in vitro are hyperexcitable and display a unique epileptiform activity, a phenomenon that is reminiscent of the finding in fragile X syndrome (FXS) mouse model. Similar to the FXS model, lovastatin suppressed the epileptiform activity and audiogenic seizures in Ube3am−/p+. The in vitro model of Ube3am−/p+ is valuable for dissection of neural mechanism and epilepsy drug screening in vivo.

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Section: Resultsmentioning

confidence: 99%

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Chung

Bey

Towers

et al. 2018

Neurobiology of Disease

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“…Currently, research is focused on the understanding of action potentials and their effects on muscle and neuronal activities. Many currently investigated diseases, including Alzheimer’s disease (AD), myasthenia gravis, and epilepsy, involve the disturbances in action potential propagation [ 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

Bahar

Kim

Yoon

2016

IJMS

198

140

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The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca2+) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca2+ regulates cell death both at the early and late stages of apoptosis. Severe Ca2+ dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca2+ (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca2+ and action potential in ER stress-mediated apoptosis.

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“…Seizures are caused by synchronous, abnormal, and excessive discharge of a population of neurons. Traditionally, the mechanisms underlying the hyper-excitable state have been ascribed to synaptic alterations (increased excitatory transmission or reduced inhibitory transmission, for review [ 2 ]), voltage-gated ion channels dysfunctions (for review, [ 3 , 4 ]) or a shift in extra- or intracellular ionic concentrations in favor of membrane potential depolarization (for review [ 5 ]). The causes for these changes are incompletely understood.…”

Section: Introductionmentioning

confidence: 99%

Hungry Neurons: Metabolic Insights on Seizure Dynamics

Bazzigaluppi

Amini

Weisspapir

et al. 2017

IJMS

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Epilepsy afflicts up to 1.6% of the population and the mechanisms underlying the appearance of seizures are still not understood. In past years, many efforts have been spent trying to understand the mechanisms underlying the excessive and synchronous firing of neurons. Traditionally, attention was pointed towards synaptic (dys)function and extracellular ionic species (dys)regulation. Recently, novel clinical and preclinical studies explored the role of brain metabolism (i.e., glucose utilization) of seizures pathophysiology revealing (in most cases) reduced metabolism in the inter-ictal period and increased metabolism in the seconds preceding and during the appearance of seizures. In the present review, we summarize the clinical and preclinical observations showing metabolic dysregulation during epileptogenesis, seizure initiation, and termination, and in the inter-ictal period. Recent preclinical studies have shown that 2-Deoxyglucose (2-DG, a glycolysis blocker) is a novel therapeutic approach to reduce seizures. Furthermore, we present initial evidence for the effectiveness of 2-DG in arresting 4-Aminopyridine induced neocortical seizures in vivo in the mouse.

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The Role of Calcium Channels in Epilepsy

Cited by 80 publications

References 261 publications

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

Lovastatin suppresses hyperexcitability and seizure in Angelman syndrome model

ER Stress-Mediated Signaling: Action Potential and Ca2+ as Key Players

Hungry Neurons: Metabolic Insights on Seizure Dynamics

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