KEGG   PATHWAY: ko04261Help
ko04261                     Pathway                                

Adrenergic signaling in cardiomyocytes
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.
Organismal Systems; Circulatory system
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ko04261  Adrenergic signaling in cardiomyocytes

Ortholog table
H00720  Long QT syndrome
H00731  Atrial fibrillation
H00773  Autosomal dominant mental retardation
H01019  Catecholaminergic polymorphic ventricular tachycardia
H02091  Jervell and Lange-Nielsen syndrome
Other DBs
GO: 0001997
K04141  adrenergic receptor beta-1
K04142  adrenergic receptor beta-2
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:]
K08042  adenylate cyclase 2 [EC:]
K08043  adenylate cyclase 3 [EC:]
K08044  adenylate cyclase 4 [EC:]
K08045  adenylate cyclase 5 [EC:]
K08046  adenylate cyclase 6 [EC:]
K08047  adenylate cyclase 7 [EC:]
K08048  adenylate cyclase 8 [EC:]
K08049  adenylate cyclase 9 [EC:]
K04345  protein kinase A [EC:]
K01539  sodium/potassium-transporting ATPase subunit alpha [EC:]
K01540  sodium/potassium-transporting ATPase subunit beta
K01538  sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K05742  solute carrier family 9 (sodium/hydrogen exchanger), member 1
K04926  potassium voltage-gated channel KQT-like subfamily member 1
K04894  potassium voltage-gated channel Isk-related subfamily E member 1
K05850  P-type Ca2+ transporter type 2B [EC:]
K05849  solute carrier family 8 (sodium/calcium exchanger)
K04838  voltage-gated sodium channel type V alpha
K04839  voltage-gated sodium channel type VII alpha
K04845  voltage-gated sodium channel type I beta
K04848  voltage-gated sodium channel type IV beta
K04850  voltage-dependent calcium channel L type alpha-1C
K04851  voltage-dependent calcium channel L type alpha-1D
K04853  voltage-dependent calcium channel L type alpha-1F
K04857  voltage-dependent calcium channel L type alpha-1S
K04862  voltage-dependent calcium channel beta-1
K04863  voltage-dependent calcium channel beta-2
K04864  voltage-dependent calcium channel beta-3
K04865  voltage-dependent calcium channel beta-4
K04858  voltage-dependent calcium channel alpha-2/delta-1
K04859  voltage-dependent calcium channel alpha-2/delta-2
K04860  voltage-dependent calcium channel alpha-2/delta-3
K04861  voltage-dependent calcium channel alpha-2/delta-4
K04866  voltage-dependent calcium channel gamma-1
K04867  voltage-dependent calcium channel gamma-2
K04868  voltage-dependent calcium channel gamma-3
K04869  voltage-dependent calcium channel gamma-4
K04870  voltage-dependent calcium channel gamma-5
K04871  voltage-dependent calcium channel gamma-6
K04872  voltage-dependent calcium channel gamma-7
K04873  voltage-dependent calcium channel gamma-8
K02183  calmodulin
K04515  calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:]
K04962  ryanodine receptor 2
K04382  serine/threonine-protein phosphatase 2A catalytic subunit [EC:]
K03456  serine/threonine-protein phosphatase 2A regulatory subunit A
K04354  serine/threonine-protein phosphatase 2A regulatory subunit B
K11583  serine/threonine-protein phosphatase 2A regulatory subunit B''
K11584  serine/threonine-protein phosphatase 2A regulatory subunit B'
K06269  serine/threonine-protein phosphatase PP1 catalytic subunit [EC:]
K05865  troponin C, slow skeletal and cardiac muscles
K12044  troponin I, cardiac muscle
K12045  troponin T, cardiac muscle
K10373  tropomyosin 1
K10374  tropomyosin 2
K09290  tropomyosin 3
K10375  tropomyosin 4
K12314  actin, alpha cardiac muscle
K17751  myosin heavy chain 6/7
K10351  myosin regulatory light chain 2
K12749  myosin light chain 3
K12750  myosin light chain 4
K05852  phospholamban
K05853  P-type Ca2+ transporter type 2A [EC:]
K09821  angiotensinogen
K04166  angiotensin II receptor type 1
K04167  angiotensin II receptor type 2
K04135  adrenergic receptor alpha-1A
K04136  adrenergic receptor alpha-1B
K04137  adrenergic receptor alpha-1D
K04634  guanine nucleotide-binding protein G(q) subunit alpha
K05858  phosphatidylinositol phospholipase C, beta [EC:]
K02677  classical protein kinase C alpha type [EC:]
K08050  protein phosphatase 1 regulatory subunit 1A
K04371  mitogen-activated protein kinase 1/3 [EC:]
K04445  ribosomal protein S6 kinase alpha-5 [EC:]
K05870  cyclic AMP-responsive element-binding protein 1
K04450  cyclic AMP-dependent transcription factor ATF-2
K04374  cyclic AMP-dependent transcription factor ATF-4
K09048  cyclic AMP-responsive element-binding protein 3
K09047  cyclic AMP-responsive element-binding protein 5
K09049  cyclic AMP-dependent transcription factor ATF-6 beta
K09052  cAMP response element modulator
K02161  apoptosis regulator Bcl-2
K08014  Rap guanine nucleotide exchange factor 3
K04351  Rap guanine nucleotide exchange factor 4
K04441  p38 MAP kinase [EC:]
K04630  guanine nucleotide-binding protein G(i) subunit alpha
K21289  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [EC:]
K21290  phosphoinositide-3-kinase regulatory subunit 5/6
K04456  RAC serine/threonine-protein kinase [EC:]
C00076  Calcium cation
C00080  H+
C00165  Diacylglycerol
C00238  Potassium cation
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00788  L-Adrenaline
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C07056  Isoproterenol
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J Mol Cell Cardiol 48:322-30 (2010)
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Anger, emotion, and arrhythmias: from brain to heart.
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Herz 27:683-90 (2002)
Xiao RP
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Sci STKE 2001:re15 (2001)
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Nature 415:198-205 (2002)
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Prog Biophys Mol Biol 85:261-78 (2004)
Yano M, Ikeda Y, Matsuzaki M
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J Clin Invest 115:556-64 (2005)
Wehrens XH, Marks AR
Novel therapeutic approaches for heart failure by normalizing calcium cycling.
Nat Rev Drug Discov 3:565-73 (2004)
Triposkiadis F, Karayannis G, Giamouzis G, Skoularigis J, Louridas G, Butler J
The sympathetic nervous system in heart failure physiology, pathophysiology, and clinical implications.
J Am Coll Cardiol 54:1747-62 (2009)
Barry SP, Davidson SM, Townsend PA
Molecular regulation of cardiac hypertrophy.
Int J Biochem Cell Biol 40:2023-39 (2008)

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