Full Text Journal Articles by
Author Peter C Ruben

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Cannabidiol and Sodium Channel Pharmacology: General Overview, Mechanism, and Clinical Implications.

Mohammad-Reza Ghovanloo, Peter C Ruben,

Voltage-gated sodium (Nav) channels initiate action potentials in excitable tissues. Altering these channels' function can lead to many pathophysiological conditions. Nav channels are composed of several functional and structural domains that could be targeted pharmacologically as potential therapeutic means against various neurological conditions. Mutations in Nav channels have been suggested ... Read more >>

Neuroscientist (The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry)
[2021, :10738584211017009]

Cited: 0 times

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Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity.

Mohammad-Reza Ghovanloo, Koushik Choudhury, Tagore S Bandaru, Mohamed A Fouda, Kaveh Rayani, Radda Rusinova, Tejas Phaterpekar, Karen Nelkenbrecher, Abeline R Watkins, Damon Poburko, Jenifer Thewalt, Olaf S Andersen, Lucie Delemotte, Samuel J Goodchild, Peter C Ruben,

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal ... Read more >>

J Gen Physiol (The Journal of general physiology)
[2021, 153(5):]

Cited: 0 times

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Protein Kinases Mediate Anti-Inflammatory Effects of Cannabidiol and Estradiol Against High Glucose in Cardiac Sodium Channels.

Mohamed A Fouda, Peter C Ruben,

<b>Background:</b> Cardiovascular anomalies are predisposing factors for diabetes-induced morbidity and mortality. Recently, we showed that high glucose induces changes in the biophysical properties of the cardiac voltage-gated sodium channel (Nav1.5) that could be strongly correlated to diabetes-induced arrhythmia. However, the mechanisms underlying hyperglycemia-induced inflammation, and how inflammation provokes cardiac arrhythmia, ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2021, 12:668657]

Cited: 1 time

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Cannabidiol interactions with voltage-gated sodium channels.

Lily Goodyer Sait, Altin Sula, Mohammad-Reza Ghovanloo, David Hollingworth, Peter C Ruben, B A Wallace,

Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate ... Read more >>

Elife (eLife)
[2020, 9:]

Cited: 3 times

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Biophysical Characterization of a Novel SCN5A Mutation Associated With an Atypical Phenotype of Atrial and Ventricular Arrhythmias and Sudden Death.

Mohammad-Reza Ghovanloo, Joseph Atallah, Carolina A Escudero, Peter C Ruben,

<h4>Background</h4>Sudden cardiac death (SCD) is an unexpected death that occurs within an hour of the onset of symptoms. Hereditary primary electrical disorders account for up to 1/3 of all SCD cases in younger individuals and include conditions such as catecholaminergic polymorphic ventricular tachycardia (CPVT). These disorders are caused by mutations ... Read more >>

Front Physiol (Frontiers in physiology)
[2020, 11:610436]

Cited: 1 time

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Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels.

Mohamed A Fouda, Mohammad-Reza Ghovanloo, Peter C Ruben,

<h4>Background and purpose</h4>Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetes-associated arrhythmias are unclear. We hypothesized that high glucose could adversely affect Na<sub>v</sub> 1.5, the major cardiac sodium channel isoform of the heart, at least partially via oxidative stress. We further hypothesized ... Read more >>

Br J Pharmacol (British journal of pharmacology)
[2020, 177(13):2932-2946]

Cited: 7 times

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Say Cheese: Structure of the Cardiac Electrical Engine Is Captured.

Mohammad-Reza Ghovanloo, Peter C Ruben,

Voltage-gated sodium channel (Nav)1.5 is the predominantly expressed sodium channel in the myocardium. Mutations in the gene encoding Nav1.5 are associated with several types of cardiac arrhythmias. In their recent study, Jiang et al. provide a detailed structure of the rat Nav1.5, with major implications regarding its physiology, pharmacology, and ... Read more >>

Trends Biochem Sci (Trends in biochemical sciences)
[2020, 45(5):369-371]

Cited: 2 times

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Case studies in neuroscience: a novel amino acid duplication in the NH2-terminus of the brain sodium channel NaV1.1 underlying Dravet syndrome.

Madeline Angus, Colin H Peters, Damon Poburko, Elise Brimble, Emily M Spelbrink, Peter C Ruben,

Dravet syndrome is a severe form of childhood epilepsy characterized by frequent temperature-sensitive seizures and delays in cognitive development. In the majority (80%) of cases, Dravet syndrome is caused by mutations in the SCN1A gene, encoding the voltage-gated sodium channel Na<sub>V</sub>1.1, which is abundant in the central nervous system. Dravet ... Read more >>

J Neurophysiol (Journal of neurophysiology)
[2019, 122(5):1975-1980]

Cited: 0 times

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Inhibitory effects of cannabidiol on voltage-dependent sodium currents.

Mohammad-Reza Ghovanloo, Noah Gregory Shuart, Janette Mezeyova, Richard A Dean, Peter C Ruben, Samuel J Goodchild,

<i>Cannabis sativa</i> contains many related compounds known as phytocannabinoids. The main psychoactive and nonpsychoactive compounds are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), respectively. Much of the evidence for clinical efficacy of CBD-mediated antiepileptic effects has been from case reports or smaller surveys. The mechanisms for CBD's anticonvulsant effects are unclear and ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2018, 293(43):16546-16558]

Cited: 29 times

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SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Alban-Elouen Baruteau, Florence Kyndt, Elijah R Behr, Arja S Vink, Matthias Lachaud, Anna Joong, Jean-Jacques Schott, Minoru Horie, Isabelle Denjoy, Lia Crotti, Wataru Shimizu, Johan M Bos, Elizabeth A Stephenson, Leonie Wong, Dominic J Abrams, Andrew M Davis, Annika Winbo, Anne M Dubin, Shubhayan Sanatani, Leonardo Liberman, Juan Pablo Kaski, Boris Rudic, Sit Yee Kwok, Claudine Rieubland, Jacob Tfelt-Hansen, George F Van Hare, Béatrice Guyomarc'h-Delasalle, Nico A Blom, Yanushi D Wijeyeratne, Jean-Baptiste Gourraud, Hervé Le Marec, Junichi Ozawa, Véronique Fressart, Jean-Marc Lupoglazoff, Federica Dagradi, Carla Spazzolini, Takeshi Aiba, David J Tester, Laura A Zahavich, Virginie Beauséjour-Ladouceur, Mangesh Jadhav, Jonathan R Skinner, Sonia Franciosi, Andrew D Krahn, Mena Abdelsayed, Peter C Ruben, Tak-Cheung Yung, Michael J Ackerman, Arthur A Wilde, Peter J Schwartz, Vincent Probst,

<h4>Aims</h4>To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.<h4>Methods and results</h4>A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation ... Read more >>

Eur Heart J (European heart journal)
[2018, 39(31):2879-2887]

Cited: 6 times

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A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels.

Mohammad-Reza Ghovanloo, Mena Abdelsayed, Colin H Peters, Peter C Ruben,

Skeletal muscle channelopathies, many of which are inherited as autosomal dominant mutations, include myotonia and periodic paralysis. Myotonia is defined by a delayed relaxation after muscular contraction, whereas periodic paralysis is defined by episodic attacks of weakness. One sub-type of periodic paralysis, known as hypokalemic periodic paralysis (hypoPP), is associated ... Read more >>

Sci Rep (Scientific reports)
[2018, 8(1):6304]

Cited: 4 times

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pH Modulation of Voltage-Gated Sodium Channels.

Colin H Peters, Mohammad-Reza Ghovanloo, Cynthia Gershome, Peter C Ruben,

Changes in blood and tissue pH accompany physiological and pathophysiological conditions including exercise, cardiac ischemia, ischemic stroke, and cocaine ingestion. These conditions are known to trigger the symptoms of electrical diseases in patients carrying sodium channel mutations. Protons cause a diverse set of changes to sodium channel gating, which generally ... Read more >>

Handb Exp Pharmacol (Handbook of experimental pharmacology)
[2018, 246:147-160]

Cited: 3 times

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Effects of acidosis on neuronal voltage-gated sodium channels: Nav1.1 and Nav1.3.

Mohammad-Reza Ghovanloo, Colin H Peters, Peter C Ruben,

Voltage-gated sodium channels are key contributors to membrane excitability. These channels are expressed in a tissue-specific manner. Mutations and modulation of these channels underlie various physiological and pathophysiological manifestations. The effects of changes in extracellular pH on channel gating have been studied on several sodium channel subtypes. Among these, Nav1.5 ... Read more >>

Channels (Austin) (Channels (Austin, Tex.))
[2018, 12(1):367-377]

Cited: 3 times

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Differential calcium sensitivity in NaV 1.5 mixed syndrome mutants.

Mena Abdelsayed, Alban-Elouen Baruteau, Karen Gibbs, Shubhayan Sanatani, Andrew D Krahn, Vincent Probst, Peter C Ruben,

<h4>Key points</h4>SCN5a mutations may express gain-of-function (Long QT Syndrome-3), loss-of-function (Brugada Syndrome 1) or both (mixed syndromes), depending on the mutation and environmental triggers. One such trigger may be an increase in cytosolic calcium, accompanying exercise. Many mixed syndromes mutants, including ∆KPQ, E1784K, 1795insD and Q1909R, are found in calcium-sensitive ... Read more >>

J Physiol (The Journal of physiology)
[2017, 595(18):6165-6186]

Cited: 9 times

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Triggers for arrhythmogenesis in the Brugada and long QT 3 syndromes.

Colin H Peters, Mena Abdelsayed, Peter C Ruben,

Cardiac arrhythmias are a prevalent cause of morbidity and mortality. In many cases, inheritable mutations in the genes encoding cardiac ion channels are the underlying cause of arrhythmias. Relative to other arrhythmogenic disorders, Brugada syndrome (BrS) is recently identified and not well-understood. Although most often referred to as a disease ... Read more >>

Prog Biophys Mol Biol (Progress in biophysics and molecular biology)
[2016, 120(1-3):77-88]

Cited: 11 times

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Effects of Amiodarone and N-desethylamiodarone on Cardiac Voltage-Gated Sodium Channels.

Mohammad-Reza Ghovanloo, Mena Abdelsayed, Peter C Ruben,

Amiodarone (AMD) is a potent antiarrhythmic drug with high efficacy for treating atrial fibrillation and tachycardia. The pharmacologic profile of AMD is complex. AMD possesses biophysical characteristics of all of class I, II, III, and IV agents. Despite its adverse side effects, AMD remains the most commonly prescribed antiarrhythmic drug. ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2016, 7:39]

Cited: 10 times

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Differential thermosensitivity in mixed syndrome cardiac sodium channel mutants.

Mena Abdelsayed, Colin H Peters, Peter C Ruben,

Cardiac arrhythmias are often associated with mutations in SCN5A the gene that encodes the cardiac paralogue of the voltage-gated sodium channel, NaV 1.5. The NaV 1.5 mutants R1193Q and E1784K give rise to both long QT and Brugada syndromes. Various environmental factors, including temperature, may unmask arrhythmia. We sought to ... Read more >>

J Physiol (The Journal of physiology)
[2015, 593(18):4201-4223]

Cited: 18 times

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Introduction to sodium channels.

Colin H Peters, Peter C Ruben,

Voltage-gated sodium channels (VGSCs) are present in many tissue types within the human body including both cardiac and neuronal tissues. Like other channels, VGSCs activate, deactivate, and inactivate in response to changes in membrane potential. VGSCs also have a similar structure to other channels: 24 transmembrane segments arranged into four ... Read more >>

Handb Exp Pharmacol (Handbook of experimental pharmacology)
[2014, 221:1-6]

Cited: 6 times

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Proton modulation of cardiac I Na: a potential arrhythmogenic trigger.

David K Jones, Peter C Ruben,

Voltage-gated sodium (NaV) channels generate the upstroke and mediate duration of the ventricular action potential, thus they play a critical role in mediating cardiac excitability. Cardiac ischemia triggers extracellular pH to drop as low as pH 6.0, within just 10 min of its onset. Heightened proton concentrations reduce sodium conductance ... Read more >>

Handb Exp Pharmacol (Handbook of experimental pharmacology)
[2014, 221:169-181]

Cited: 5 times

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A thermosensitive mutation alters the effects of lacosamide on slow inactivation in neuronal voltage-gated sodium channels, NaV1.2.

Mena Abdelsayed, Stanislav Sokolov, Peter C Ruben,

Epilepsy is a disorder characterized by seizures and convulsions. The basis of epilepsy is an increase in neuronal excitability that, in some cases, may be caused by functional defects in neuronal voltage gated sodium channels (NaVs). The C121W mutation of the β1 subunit, in particular, gives rise to the thermosensitive ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2013, 4:121]

Cited: 2 times

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Proton sensors in the pore domain of the cardiac voltage-gated sodium channel.

David K Jones, Colin H Peters, Charlene R Allard, Tom W Claydon, Peter C Ruben,

Protons impart isoform-specific modulation of inactivation in neuronal, skeletal muscle, and cardiac voltage-gated sodium (Na(V)) channels. Although the structural basis of proton block in Na(V) channels has been well described, the amino acid residues responsible for the changes in Na(V) kinetics during extracellular acidosis are as yet unknown. We expressed ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2013, 288(7):4782-4791]

Cited: 8 times

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A hot topic: temperature sensitive sodium channelopathies.

Csilla Egri, Peter C Ruben,

Perturbations to body temperature affect almost all cellular processes and, within certain limits, results in minimal effects on overall physiology. Genetic mutations to ion channels, or channelopathies, can shift the fine homeostatic balance resulting in a decreased threshold to temperature induced disturbances. This review summarizes the functional consequences of currently ... Read more >>

Channels (Austin) (Channels (Austin, Tex.))
[2012, 6(2):75-85]

Cited: 5 times

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A thermoprotective role of the sodium channel β1 subunit is lost with the β1 (C121W) mutation.

Csilla Egri, Yuriy Y Vilin, Peter C Ruben,

<h4>Purpose</h4>A mutation in the β(1) subunit of the voltage-gated sodium (Na(V)) channel, β(1) (C121W), causes genetic epilepsy with febrile seizures plus (GEFS+), a pediatric syndrome in which febrile seizures are the predominant phenotype. Previous studies of molecular mechanisms underlying neuronal hyperexcitability caused by this mutation were conducted at room temperature. ... Read more >>

Epilepsia (Epilepsia)
[2012, 53(3):494-505]

Cited: 12 times

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Acidosis differentially modulates inactivation in na(v)1.2, na(v)1.4, and na(v)1.5 channels.

Yury Y Vilin, Colin H Peters, Peter C Ruben,

Na(V) channels play a crucial role in neuronal and muscle excitability. Using whole-cell recordings we studied effects of low extracellular pH on the biophysical properties of Na(V)1.2, Na(V)1.4, and Na(V)1.5, expressed in cultured mammalian cells. Low pH produced different effects on different channel subtypes. Whereas Na(V)1.4 exhibited very low sensitivity ... Read more >>

Front Pharmacol (Frontiers in pharmacology)
[2012, 3:109]

Cited: 16 times

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Biophysical costs associated with tetrodotoxin resistance in the sodium channel pore of the garter snake, Thamnophis sirtalis.

Chong Hyun Lee, David K Jones, Christopher Ahern, Maen F Sarhan, Peter C Ruben,

Tetrodotoxin (TTX) is a potent toxin that specifically binds to voltage-gated sodium channels (NaV). TTX binding physically blocks the flow of sodium ions through NaV, thereby preventing action potential generation and propagation. TTX has different binding affinities for different NaV isoforms. These differences are imparted by amino acid substitutions in ... Read more >>

J Comp Physiol A Neuroethol Sens Neural Behav Physiol (Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology)
[2011, 197(1):33-43]

Cited: 5 times

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