CaMKII in Cardiac Health and Disease

The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional me...

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Prif Awduron: Andrew G Edwards, Donald M Bers, Eleonora Grandi, Anthony W Herren
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Cyhoeddwyd: Frontiers Media SA 2021
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Mynediad Ar-lein:17850
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author Andrew G Edwards
Donald M Bers
Eleonora Grandi
Anthony W Herren
author_browse Andrew G Edwards
Anthony W Herren
Donald M Bers
Eleonora Grandi
author_facet Andrew G Edwards
Donald M Bers
Eleonora Grandi
Anthony W Herren
author_sort Andrew G Edwards
collection Directory of Open Access Books
description The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology.
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spelling doab-20.500.12854ir-426092024-04-01T14:15:21Z CaMKII in Cardiac Health and Disease Andrew G Edwards Donald M Bers Eleonora Grandi Anthony W Herren RC346-429 R5-920 RM1-950 Q1-390 Phosphorylation Ion Channels Calcium arrhythmia Heart Failure Hypertrophy thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology The calcium-calmodulin dependent protein kinases (CaMKs) are a broadly expressed family of calcium-sensitive intracellular kinases, which are responsible for transducing cytosolic calcium signals into phosphorylation-based regulation of proteins and physiological functions. As the multifunctional member of the family, CaMKII has become the most prominent for its roles in the central nervous system and heart, where it controls a diverse range of calcium-dependent processes; from learning and memory at the neuronal synapse, to cellular growth and death in the myocardium. In the heart, CaMKII directly regulates many of the most important ion channels and calcium handling proteins, and controls the expression of an ever-increasing number of transcripts and their downstream products. Functionally, these actions are thought to orchestrate many of the electrophysiologic and contractile adaptations to common cardiac stressors, such as rapid pacing, chronic adrenergic stimulation, and oxidative challenge. In the context of disease, CaMKII has been shown to contribute to a remarkably wide variety of cardiac pathologies, of which heart failure (HF) is the most conspicuous. Hyperactivity of CaMKII is an established contributor to pathological cardiac remodeling, and is widely thought to directly promote arrhythmia and contractile dysfunction during HF. Moreover, several non-failing arrhythmia-susceptible phenotypes, which result from specific genetic channelopathies, functionally mimic constitutive channel phosphorylation by CaMKII. Because CaMKII contributes to both the acute and chronic manifestations of major cardiac diseases, but may be only minimally required for homeostasis in the absence of chronic stress, it has come to be one of the most promising therapeutic drug targets in cardiac biology. Thus, development of more specific and deliverable small molecule antagonists remains a key priority for the field. Here we provide a selection of articles to summarize the state of our knowledge regarding CaMKII in cardiac health and disease, with a particular view to highlighting recent developments in CaMKII activation, and new targets in CaMKII-mediated control of myocyte physiology. 2021-02-11T09:26:03Z 2021-02-11T09:26:03Z 2015-12-10 11:59:07 2014 book 17850 16648714 9782889192991 https://directory.doabooks.org/handle/20.500.12854/42609 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/CaMKII_in_Cardiac_Health_and_Disease/331 http://journal.frontiersin.org/researchtopic/1820/camkii-in-cardiac-health-and-disease Frontiers Media SA 10.3389/978-2-88919-299-1 10.3389/978-2-88919-299-1 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889192991 165 open access
spellingShingle RC346-429
R5-920
RM1-950
Q1-390
Phosphorylation
Ion Channels
Calcium
arrhythmia
Heart Failure
Hypertrophy
thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
Andrew G Edwards
Donald M Bers
Eleonora Grandi
Anthony W Herren
CaMKII in Cardiac Health and Disease
title CaMKII in Cardiac Health and Disease
title_full CaMKII in Cardiac Health and Disease
title_fullStr CaMKII in Cardiac Health and Disease
title_full_unstemmed CaMKII in Cardiac Health and Disease
title_short CaMKII in Cardiac Health and Disease
title_sort camkii in cardiac health and disease
topic RC346-429
R5-920
RM1-950
Q1-390
Phosphorylation
Ion Channels
Calcium
arrhythmia
Heart Failure
Hypertrophy
thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
topic_facet RC346-429
R5-920
RM1-950
Q1-390
Phosphorylation
Ion Channels
Calcium
arrhythmia
Heart Failure
Hypertrophy
thema EDItEUR::M Medicine and Nursing::MK Medical specialties, branches of medicine::MKJ Neurology and clinical neurophysiology
url 17850
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AT donaldmbers camkiiincardiachealthanddisease
AT eleonoragrandi camkiiincardiachealthanddisease
AT anthonywherren camkiiincardiachealthanddisease