Entry
Name
Adrenergic signaling in cardiomyocytes - Myotis brandtii (Brandt's bat)
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
myb04261 Adrenergic signaling in cardiomyocytes
Ortholog table
Other DBs
Organism
Myotis brandtii (Brandt's bat) [GN:
myb ]
Gene
102252262 guanine nucleotide-binding protein G(s) subunit alpha isoforms short [KO:K04632 ]
102243046 ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540 ]
102246906 KCNE1; potassium voltage-gated channel subfamily E member 1 [KO:K04894 ]
102240225 CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850 ]
102259218 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
102260789 CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853 ]
102243265 CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857 ]
102247800 CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862 ]
102243843 CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863 ]
102247877 CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864 ]
102261332 CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865 ]
102238945 CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858 ]
102239809 CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859 ]
102239827 voltage-dependent calcium channel subunit alpha-2/delta-3 [KO:K04860 ]
102254288 CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861 ]
102259942 CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866 ]
102244899 CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867 ]
102240803 CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868 ]
102244082 CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869 ]
102260251 CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870 ]
102252645 CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871 ]
102249601 CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872 ]
102260757 CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873 ]
102262643 PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456 ]
102254517 PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456 ]
102243537 PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354 ]
102240425 PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354 ]
102238990 PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354 ]
102254637 PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354 ]
102248512 PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583 ]
106725200 serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583 ]
102240816 PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583 ]
102241218 PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584 ]
102242374 PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584 ]
102239026 PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584 ]
102249194 PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584 ]
102244211 PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584 ]
102238678 PPP1R1A; protein phosphatase 1 regulatory inhibitor subunit 1A [KO:K08050 ]
102258024 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
102244833 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
102245296 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
102251355 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
102246489 PIK3R5; phosphoinositide-3-kinase regulatory subunit 5 [KO:K21290 ]
102246179 PIK3R6; phosphoinositide-3-kinase regulatory subunit 6 [KO:K21290 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference
Authors
Grimm M, Brown JH
Title
Beta-adrenergic receptor signaling in the heart: role of CaMKII.
Journal
Reference
Authors
Yang JH, Saucerman JJ
Title
Computational models reduce complexity and accelerate insight into cardiac signaling networks.
Journal
Reference
Authors
Schaub MC, Hefti MA, Zaugg M
Title
Integration of calcium with the signaling network in cardiac myocytes.
Journal
Reference
Authors
Taggart P, Boyett MR, Logantha S, Lambiase PD
Title
Anger, emotion, and arrhythmias: from brain to heart.
Journal
Reference
Authors
Bers DM
Title
Calcium cycling and signaling in cardiac myocytes.
Journal
Reference
Authors
Soltis AR, Saucerman JJ
Title
Synergy between CaMKII substrates and beta-adrenergic signaling in regulation of cardiac myocyte Ca(2+) handling.
Journal
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.
Journal
Reference
Authors
Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG
Title
Recent advances in cardiac beta(2)-adrenergic signal transduction.
Journal
Reference
Authors
Zheng M, Zhu W, Han Q, Xiao RP
Title
Emerging concepts and therapeutic implications of beta-adrenergic receptor subtype signaling.
Journal
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.
Journal
Reference
Authors
Bers DM
Title
Cardiac excitation-contraction coupling.
Journal
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.
Journal
Reference
Authors
Saucerman JJ, McCulloch AD
Title
Mechanistic systems models of cell signaling networks: a case study of myocyte adrenergic regulation.
Journal
Reference
Authors
Yano M, Ikeda Y, Matsuzaki M
Title
Altered intracellular Ca2+ handling in heart failure.
Journal
Reference
Authors
Wehrens XH, Marks AR
Title
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
Journal
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
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