Ion channel trafficking implications in heart failure

Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%-2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survi...

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Published inFrontiers in cardiovascular medicine Vol. 11; p. 1351496
Main Authors Reisqs, Jean-Baptiste, Qu, Yongxia Sarah, Boutjdir, Mohamed
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 14.02.2024
Subjects
arrhythmia
Cardiovascular Medicine
electrophysiology
heart failure
ion channels
trafficking
treatment
heart failure
treatment
electrophysiology
trafficking
arrhythmia
ion channels
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Summary:Heart failure (HF) is recognized as an epidemic in the contemporary world, impacting around 1%-2% of the adult population and affecting around 6 million Americans. HF remains a major cause of mortality, morbidity, and poor quality of life. Several therapies are used to treat HF and improve the survival of patients; however, despite these substantial improvements in treating HF, the incidence of HF is increasing rapidly, posing a significant burden to human health. The total cost of care for HF is USD 69.8 billion in 2023, warranting a better understanding of the mechanisms involved in HF. Among the most serious manifestations associated with HF is arrhythmia due to the electrophysiological changes within the cardiomyocyte. Among these electrophysiological changes, disruptions in sodium and potassium currents' function and trafficking, as well as calcium handling, all of which impact arrhythmia in HF. The mechanisms responsible for the trafficking, anchoring, organization, and recycling of ion channels at the plasma membrane seem to be significant contributors to ion channels dysfunction in HF. Variants, microtubule alterations, or disturbances of anchoring proteins lead to ion channel trafficking defects and the alteration of the cardiomyocyte's electrophysiology. Understanding the mechanisms of ion channels trafficking could provide new therapeutic approaches for the treatment of HF. This review provides an overview of the recent advances in ion channel trafficking in HF.
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Reviewed by: Florentina Pluteanu, University of Bucharest, Romania
Edited by: Hua-Qian Yang, Soochow University, China
Przemyslaw Radwanski, The Ohio State University, United States
Abbreviations AAV, adeno-associated virus; AP, action potential; APD, action potential duration; ATF6, activating transcription factor 6; Ca2+, calcium; CAMKII, calmodulin-dependent kinase II; CASK, calcium/calmodulin-dependent serine protein kinase; COP, coatomer protein; Cx43, connexin-43; DAD, delayed afterdepolarization; EAD, early afterdepolarization; EB1, plus-end binding protein; EF, ejection fraction; ER, endoplasmic reticulum; ERAD, ER-associated degradation system; ERES, endoplasmic reticulum exit site; hERG, human ether-a-go-go–related gene; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; hiPSC, human-induced pluripotent stem cells; HSP, heat shock protein; ICaL, L-type calcium current; If, funny current; IK1, inwardly rectifying potassium current; IKr, rapid outward potassium current; IKs, slow outward potassium current; INa, sodium current; INaL, late sodium current; Ito, transient outward potassium current; IRE1, inositol-requiring enzyme 1; KCNQ1, potassium voltage-gated subfamily Q member 1; MAGUK, membrane-associated guanylate kinase; MLP, Muscle Lim Protein; MRA, mineralocorticoid receptor antagonist; Na+, sodium; NCX, Na+/Ca2+ exchanger; NHE, Na+/H+ exchanger; NSF, N-ethylmaleimide sensitive fusion protein; PERK, protein kinase R-like ER kinase; PKA, protein kinase A; PKC, protein kinase C; ROS, reactive oxygen species; RYR, ryanodine receptor; SAP97, synapse-associated protein 97; SERCA, sarcoplasmic reticulum Ca2+-ATPase; SGLT2, sodium-glucose cotransporter 2; SNAP, NSF attachment protein; SNARE, SNAP receptor; SR, sarcoplasmic reticulum; UPR, unfolded protein response.
ISSN:2297-055X
2297-055X
DOI:10.3389/fcvm.2024.1351496