Ion Channels in the Heart

Bartos, Daniel C.; Grandi, Eleonora; Ripplinger, Crystal M.

doi:10.1002/cphy.c140069

Cited by 152 publications

(170 citation statements)

References 606 publications

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“…During cardiac action potentials, there is a flux of sodium (Na + ) into the cell, along with an inward flux of calcium (Ca + ), that leads to the depolarization, followed by outward potassium (K + ) currents that repolarize the cell (1,(8)(9)(10)(11)). …”

Section: Action Potentials Drive Heart Beatmentioning

confidence: 99%

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RNAs that make a heart beat

Mitra

Coller²

2016

Ann. Transl. Med.

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An increase in stress-associated microRNAs has been observed in the heart after an induced myocardial infarction. Liu and colleagues now demonstrate that one of these stress-associated microRNAs, miR-223-3p, can regulate a component of the voltage-gated channel that mediates rapid outward efflux of potassium during an action potential. Aberrations in the potassium current have been associated with ventricular arrhythmia and heart disease. Strikingly, introducing a small RNA antagonist directed against miR-223-3p into rat hearts, while also inducing a myocardial infarction, resulted in a reduction in arrhythmias. We place these studies in the larger context of the field and discuss the potential of anti-miR-223-3p molecules as new therapeutics for myocardial infarction.

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Section: Action Potentials Drive Heart Beatmentioning

confidence: 99%

“…An action potential is divided into several phases (1,(9)(10)(11)(12). In phase 4, the resting phase, the membrane potential of a ventricular cardiomyocyte is about −90 mV because, like most cells, ventricular cardiomyocytes have a more negative charge inside than outside of the cell.…”

Section: Action Potentials Drive Heart Beatmentioning

confidence: 99%

RNAs that make a heart beat

Mitra

Coller²

2016

Ann. Transl. Med.

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“…For example, the repolarization duration of the cardiac action potential (AP) and its correlate on the body surface, the QTinterval, are determined by a delicate balance of ion currents ( Fig. 1, top panel) [2]. If repolarization duration is too short, cells can become excitable too soon, favoring the development of reentrant tachyarrhythmias.…”

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confidence: 99%

“…If repolarization duration is too short, cells can become excitable too soon, favoring the development of reentrant tachyarrhythmias. On the other hand, if AP duration (APD) becomes too long, secondary depolarizations can develop before full repolarization (termed early afterdepolarizations; EADs), potentially creating large spatial repolarization gradients and triggering Torsades des Pointes (TdP) arrhythmias [2].…”

mentioning

confidence: 99%

“…Loss-of-function mutations in the KCNH2 gene, encoding the pore-forming subunit of the I Kr channel, represent the second-most common form of the congenital long-QT syndrome, whereas gain-of-function mutations have been associated with short-QT syndrome and familial atrial fibrillation [2,4]. In addition, many drugs have a high affinity for blocking I Kr , resulting in an acquired form of the long-QT syndrome with a significant risk of ventricular arrhythmias [3,5].…”

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confidence: 99%

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T-wave Right Slope Provides a New Angle in the Prediction of Drug-Induced Ventricular Arrhythmias

Heijman

Crijns

2015

Cardiovasc Drugs Ther

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The Application of High‐Throughput Approaches in Identifying Novel Therapeutic Targets and Agents to Treat Diabetes

Lim

2022

Advanced Biology

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An early example of HTS in drug development came from the identification of new antibiotics using 96-well microtiter plates, whereby fermentations of an established actinomycetes library were incubated with a panel of microorganisms, and after optimization, a screening capacity of 10 000 fermentation broths per week was achieved. [1] In the following decades, the rapid development of molecular biology techniques and advances in automated equipment have changed how new drugs are identified, and a variety of HTS-identified drugs have been approved to treat different diseases. [2] For a comprehensive list of HTS-identified drugs, please refer to the excellent review by Macarron et al. [2] High-throughput applications can also be combined with other unbiased "Omics" technologies used to study genomics, epigenomics, transcriptomics, proteomics, and metabolomics. [3] Diabetes is an incurable disease characterized by the inability of the body to maintain normoglycemia due to decreased sensitivity of various tissues to insulin and insufficient amounts of circulating insulin, a hormone produced by pancreatic β-cells. [4] Diabetes is associated with chronic complications, like macrovascular diseases (e.g., cardiovascular diseases) and microvascular diseases (e.g., damages in nerve, kidney, eye, and foot). [5,6] More than 537 million adults are currently living with diabetes, and this number is expected to increase to 693 million by 2045. In 2021, 6.7 million deaths worldwide were attributed to diabetes, [7] which made it the ninth leading cause of death. [8] Globally, the prevalence of diabetes also brings a heavy burden to healthcare systems, with an estimated expenditure of over 966 billion U.S. dollars per year. [7] Diabetes is generally categorized into two groups: Type I diabetes mellitus (T1DM) and Type II diabetes mellitus (T2DM), but there are still some cases that have different etiologies, such as gestational diabetes mellitus and monogenic diabetes. [9] Since the discovery of insulin in 1921, [10] significant progress has been made in diabetes pharmacotherapy and therapeutic technology; [11][12][13] however, since a permanent cure is unavailable, the discovery and development of anti-diabetic drugs is still at the forefront of diabetes research. With the rapid advancement in high-throughput omics technologies, combined with accumulated genome-wide association study (GWAS) data, a better understanding of diabetes pathophysiology may one day lead to the discovery of novel therapeutic targets. [14,15] This review will During the past decades, unprecedented progress in technologies has revolutionized traditional research methodologies. Among these, advances in highthroughput drug screening approaches have permitted the rapid identification of potential therapeutic agents from drug libraries that contain thousands or millions of molecules. Moreover, high-throughput-based therapeutic target discovery strategies can comprehensively interrogate relationships between biomolecules (e.g., gene, RNA, and protein) and diseas...

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Ion Channels in the Heart

Cited by 152 publications

References 606 publications

RNAs that make a heart beat

RNAs that make a heart beat

T-wave Right Slope Provides a New Angle in the Prediction of Drug-Induced Ventricular Arrhythmias

The Application of High‐Throughput Approaches in Identifying Novel Therapeutic Targets and Agents to Treat Diabetes

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