Entry
Name
Adrenergic signaling in cardiomyocytes
Description
Cardiac myocytes express at least six subtypes of adrenergic receptor (AR) which include three subtypes of beta-AR (beta-1, beta-2, beta-3) and three subtypes of the alpha-1-AR (alpha-1A, alpha-1B, and alpha-1C). In the human heart the beta-1-AR is the pre- dominate receptor. Acute sympathetic stimulation of cardiac beta-1-ARs induces positive inotropic and chronotropic effects, the most effective mechanism to acutely increase output of the heart, by coupling to Gs, formation of cAMP by adenylyl cyclase (AC), and PKA- dependent phosphorylation of various target proteins (e.g., ryanodine receptor [RyR]; phospholamban [PLB], troponin I [TnI], and the L-type Ca2+ channel [LTCC]). Chronic beta-1-AR stimulation is detrimental and induces cardiomyocyte hypertrophy and apoptosis. beta-2-AR coupled to Gs exerts a proapoptotic action as well as beta-1-AR, while beta-2-AR coupled to Gi exerts an antiapoptotic action.
Class
Organismal Systems; Circulatory system
BRITE hierarchy
Pathway map
map04261 Adrenergic signaling in cardiomyocytes
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Reference
Authors
Grimm M, Brown JH
Title
Beta-adrenergic receptor signaling in the heart: role of CaMKII.
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Reference
Authors
Yang JH, Saucerman JJ
Title
Computational models reduce complexity and accelerate insight into cardiac signaling networks.
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Reference
Authors
Schaub MC, Hefti MA, Zaugg M
Title
Integration of calcium with the signaling network in cardiac myocytes.
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Reference
Authors
Taggart P, Boyett MR, Logantha S, Lambiase PD
Title
Anger, emotion, and arrhythmias: from brain to heart.
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Reference
Authors
Bers DM
Title
Calcium cycling and signaling in cardiac myocytes.
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Reference
Authors
Soltis AR, Saucerman JJ
Title
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
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Reference
Authors
Wallukat G
Title
The beta-adrenergic receptors.
Journal
Reference
Authors
Xiao RP
Title
Beta-adrenergic signaling in the heart: dual coupling of the beta2-adrenergic receptor to G(s) and G(i) proteins.
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Reference
Authors
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG
Title
Recent advances in cardiac beta(2)-adrenergic signal transduction.
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Reference
Authors
Zheng M, Zhu W, Han Q, Xiao RP
Title
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling.
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Reference
Authors
Kuzumoto M, Takeuchi A, Nakai H, Oka C, Noma A, Matsuoka S
Title
Simulation analysis of intracellular Na+ and Cl- homeostasis during beta 1-adrenergic stimulation of cardiac myocyte.
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Reference
Authors
Bers DM
Title
Cardiac excitation-contraction coupling.
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Reference
Authors
Ho D, Yan L, Iwatsubo K, Vatner DE, Vatner SF
Title
Modulation of beta-adrenergic receptor signaling in heart failure and longevity: targeting adenylyl cyclase type 5.
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Reference
Authors
Saucerman JJ, McCulloch AD
Title
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.
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Reference
Authors
Yano M, Ikeda Y, Matsuzaki M
Title
Altered intracellular Ca2+ handling in heart failure.
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Reference
Authors
Wehrens XH, Marks AR
Title
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
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Reference
Authors
Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J
Title
The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
Journal
Reference
Authors
Barry SP, Davidson SM, Townsend PA
Title
Molecular regulation of cardiac hypertrophy.
Journal
Related pathway
KO pathway