scholarly journals Antiepileptic Drug Tiagabine Does Not Directly Target Key Cardiac Ion Channels Kv11.1, Nav1.5 and Cav1.2

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3522
Author(s):  
Magdalena Kowalska ◽  
Łukasz Fijałkowski ◽  
Monika Kubacka ◽  
Kinga Sałat ◽  
Grzegorz Grześk ◽  
...  
Keyword(s):  
Ion Channels ◽  
Adverse Effects ◽  
Antiepileptic Drug ◽  
Chemical Interaction ◽  
Cardiac Complications ◽  
Cardiac Ion Channels ◽  
Numerical Studies ◽  
Docking Method ◽  
Voltage Gated Ion Channels

Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia—an impairment of cardiac rhythm due to cardiac ion channel dysfunction—is one of the most commonly reported non-neurological adverse effects of this drug, in the present paper we have undertaken pharmacological and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chemical interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the molecular docking method. The obtained in silico results imply that the adverse effects reported so far in the clinical cardiological of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (electrocardiogram study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.

scholarly journals Proper Voltage-Dependent Ion Channel Function in Dysferlin-Deficient Cardiomyocytes

2015 ◽  
Vol 36 (3) ◽  
pp. 1049-1058 ◽  
Author(s):  
Lena Rubi ◽  
Vaibhavkumar S. Gawali ◽  
Helmut Kubista ◽  
Hannes Todt ◽  
Karlheinz Hilber ◽  
...  
Keyword(s):  
Ion Channels ◽  
Muscular Dystrophy ◽  
Ion Channel ◽  
Cardiac Electrophysiology ◽  
Cardiac Complications ◽  
Membrane Repair ◽  
Patch Clamp Technique ◽  
Cardiac Ion Channels ◽  
Ventricular Cardiomyocytes ◽  
Voltage Dependent

Background/Aims: Dysferlin plays a decisive role in calcium-dependent membrane repair in myocytes. Mutations in the encoding DYSF gene cause a number of myopathies, e.g. limb-girdle muscular dystrophy type 2B (LGMD2B). Besides skeletal muscle degenerative processes, dysferlin deficiency is also associated with cardiac complications. Thus, both LGMD2B patients and dysferlin-deficient mice develop a dilated cardiomyopathy. We and others have recently reported that dystrophin-deficient ventricular cardiomyocytes from mouse models of Duchenne muscular dystrophy show significant abnormalities in voltage-dependent ion channels, which may contribute to the pathophysiology in dystrophic cardiomyopathy. The aim of the present study was to investigate if dysferlin, like dystrophin, is a regulator of cardiac ion channels. Methods and Results: By using the whole cell patch-clamp technique, we compared the properties of voltage-dependent calcium and sodium channels, as well as action potentials in ventricular cardiomyocytes isolated from the hearts of normal and dysferlin-deficient (dysf) mice. In contrast to dystrophin deficiency, the lack of dysferlin did not impair the ion channel properties and left action potential parameters unaltered. In connection with normal ECGs in dysf mice these results suggest that dysferlin deficiency does not perturb cardiac electrophysiology. Conclusion: Our study demonstrates that dysferlin does not regulate cardiac voltage-dependent ion channels, and implies that abnormalities in cardiac ion channels are not a universal characteristic of all muscular dystrophy types.

scholarly journals Polyunsaturated fatty acid analogues differentially affect cardiac NaV, CaV, and KV channels through unique mechanisms

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Briana M Bohannon ◽  
Alicia de la Cruz ◽  
Xiaoan Wu ◽  
Jessica J Jowais ◽  
Marta E Perez ◽  
...  
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Induced Pluripotent Stem Cell ◽  
Voltage Gated ◽  
Kv Channels ◽  
Cardiac Ion Channels ◽  
Induced Pluripotent ◽  
Voltage Gated Ion Channels ◽  
Ventricular Action Potential ◽  
Gated Ion Channels

The cardiac ventricular action potential depends on several voltage-gated ion channels, including NaV, CaV, and KV channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating cardiac ion channels from all three families (NaV, CaV, and KV). In addition, a PUFA analogue selective for the cardiac IKs channel (Kv7.1/KCNE1) is effective in shortening the cardiac action potential in human-induced pluripotent stem cell-derived cardiomyocytes. Our data suggest that PUFA analogues could potentially be developed as therapeutics for LQTS and cardiac arrhythmia.

scholarly journals Mining recent brain proteomic databases for ion channel phosphosite nuggets

2010 ◽  
Vol 137 (1) ◽  
pp. 3-16 ◽  
Author(s):  
Oscar Cerda ◽  
Je-Hyun Baek ◽  
James S. Trimmer
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Mammalian Brain ◽  
Phosphorylation Sites ◽  
Dynamic Regulation ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
Α Subunits

Voltage-gated ion channels underlie electrical activity of neurons and are dynamically regulated by diverse cell signaling pathways that alter their phosphorylation state. Recent global mass spectrometric–based analyses of the mouse brain phosphoproteome have yielded a treasure trove of new data as to the extent and nature of phosphorylation of numerous ion channel principal or α subunits in mammalian brain. Here we compile and review data on 347 phosphorylation sites (261 unique) on 42 different voltage-gated ion channel α subunits that were identified in these recent studies. Researchers in the ion channel field can now begin to explore the role of these novel in vivo phosphorylation sites in the dynamic regulation of the localization, activity, and expression of brain ion channels through multisite phosphorylation of their principal subunits.

scholarly journals Polyunsaturated fatty acid analogues differentially affect cardiac Nav, Cav, and Kv channels through unique mechanisms

2019 ◽  
Author(s):  
Briana M. Bohannon ◽  
Xiaoan Wu ◽  
Marta E. Perez ◽  
Sara I. Liin ◽  
H. Peter Larsson
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Voltage Gated ◽  
Kv Channels ◽  
Cardiac Ion Channels ◽  
Qt Syndrome ◽  
Voltage Gated Ion Channels ◽  
Potential Therapeutics ◽  
Ventricular Action Potential ◽  
Gated Ion Channels

AbstractThe cardiac ventricular action potential depends on several voltage-gated ion channels, including Nav, Cav, and Kv channels. Mutations in these channels can cause Long QT Syndrome (LQTS) which increases the risk for ventricular fibrillation and sudden cardiac death. Polyunsaturated fatty acids (PUFAs) have emerged as potential therapeutics for LQTS because they are modulators of voltage-gated ion channels. Here we demonstrate that PUFA analogues vary in their selectivity for human voltage-gated ion channels involved in the ventricular action potential. The effects of specific PUFA analogues range from selective for a specific ion channel to broadly modulating all three cardiac ion channels (NaV, CaL, and IKs). In addition, PUFA analogues do not modulate these channels through a shared mechanism. Our data suggest that different PUFA analogues could be tailored towards specific forms of LQTS, which are caused by mutations in distinct cardiac ion channels, and thus restore a normal ventricular action potential.

Axonal excitability: molecular basis and assessment in the clinic

2016 ◽  
Author(s):  
Susanna B. Park ◽  
Cindy S-Y. Lin ◽  
Matthew C. Kiernan
Keyword(s):  
Ion Channels ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Clinical Investigation ◽  
Resting Membrane Potential ◽  
Membrane Function ◽  
Clinical Case Studies ◽  
Axonal Excitability ◽  
Voltage Gated Ion Channels

Axonal excitability techniques were developed to assess axonal resting membrane potential and ion channel function in vivo, and thereby provide greater molecular understanding of the activity of voltage gated ion channels and ion pumps underlying nerve and membrane function. Axonal excitability studies provide complimentary information to conventional nerve conduction studies, using submaximal stimuli to examine the properties underlying the excitability of the axon. Such techniques have been developed both as a research technique to examine disease pathophysiology and as a clinical investigation technique. This chapter provides an overview of axonal excitability techniques, addressing the role of key ion channels and pumps in membrane function and highlighting examples of clinical case studies, where such techniques have been utilized, including motor neuronopathies, tracking progression of chemotherapy-induced peripheral neuropathy, and assessing treatment response in chronic inflammatory demyelinating polyneuropathy.

Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research

2007 ◽  
Vol 2 (3) ◽  
pp. 189-202 ◽  
Author(s):  
Le Jean-Yves ◽  
Ouadid-Ahidouch Halima ◽  
Soriani Olivier ◽  
Besson Pierre ◽  
Ahidouch Ahmed ◽  
...  
Keyword(s):  
Cancer Research ◽  
Ion Channels ◽  
Voltage Gated ◽  
New Targets ◽  
Anti Cancer ◽  
Voltage Gated Ion Channels ◽  
Gated Ion Channels

scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

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