KEGG   PATHWAY: hsa04260Help
Entry
hsa04260                    Pathway                                
Name
Cardiac muscle contraction - Homo sapiens (human)
Description
Contraction of the heart is a complex process initiated by the electrical excitation of cardiac myocytes (excitation-contraction coupling, ECC). In cardiac myocytes, Ca2+ influx induced by activation of voltage-dependent L-type Ca channels (DHP receptors) upon membrane depolarization triggers the release of Ca2+ via Ca2+ release channels (ryanodine receptors) of sarcoplasmic reticulum (SR) through a Ca2+ -induced Ca release (CICR) mechanism. Ca2+ ions released via the CICR mechanism diffuse through the cytosolic space to contractile proteins to bind to troponinC resulting in the release of inhibition induced by troponinI. The Ca2+ binding to troponinC thereby triggers the sliding of thin and thick filaments, that is, the activation of a crossbridge and subsequent cardiac force development and/or cell shortening. Recovery occurs as Ca2+ is pumped out of the cell by the Na+/Ca2+ exchanger (NCX) or is returned to the sarcoplasmic reticulum (SR) by sarco(endo)plasmic Ca2+ -ATPase (SERCA) pumps on the non-junctional region of the SR.
Class
Organismal Systems; Circulatory system
BRITE hierarchy
Pathway map
Cardiac muscle contraction
hsa04260

All organismsOrtholog table
Disease
H00594  
Distal muscular dystrophies
H00656  
Scapuloperoneal myopathy (SPM)
H00698  
Nemaline myopathy
H00701  
Congenital fiber type disproportion (CFTD)
H00702  
Cap myopathy
H00703  
Myosin storage myopathy (MSM)
H00728  
Brugada syndrome (BRS)
H00746  
Hypokalemic periodic paralysis (HypoPP)
H00749  
Episodic ataxias
H00775  
Familial or sporadic hemiplegic migraine
H00808  
Idiopathic generalized epilepsies (IGEs)
H00811  
Distal arthrogryposis (DA)
H00831  
Primary dystonia
H01019  
Catecholaminergic polymorphic ventricular tachycardia
H01216  
Left ventricular noncompaction (LVNC)
H01219  
Restrictive cardiomyopathy (RCM)
Drug
D00112  
G-Strophanthin (JAN)
D00297  
Digitoxin (JP16/USP/INN)
D00298  
Digoxin (JP16/USP)
D00319  
Felodipine (JAN/USP/INN)
D00349  
Isradipine (USP/INN)
D00437  
Nifedipine (JP16/USP/INN)
D00438  
Nimodipine (USAN/INN)
D00615  
Amlodipine besilate (JP16)
D00616  
Diltiazem hydrochloride (JP16/USP)
D00617  
Nicardipine hydrochloride (JP16/USAN)
D00618  
Nisoldipine (JAN/USAN/INN)
D00619  
Verapamil hydrochloride (JP16/USP)
D00629  
Nitrendipine (JP16/USAN/INN)
D00631  
Bepridil hydrochloride hydrate (JAN)
D01104  
Barnidipine hydrochloride (JAN)
D01145  
Azelnidipine (JP16/INN)
D01173  
Cilnidipine (JAN/INN)
D01240  
Deslanoside (JP16/USP/INN)
D01379  
Proscillaridin (JAN/USAN/INN)
D01553  
Manidipine hydrochloride (JP16)
D01562  
Aranidipine (JAN/INN)
D01604  
Efonidipine hydrochloride ethanolate (JAN)
D01849  
Lercanidipine hydrochloride (JAN/USAN)
D01908  
Nilvadipine (JP16/USAN/INN)
D01969  
Gallopamil hydrochloride (JAN)
D01972  
Lanatoside C (JP16/INN)
D02045  
Benidipine hydrochloride (JP16)
D02356  
Verapamil (USAN/INN)
D02537  
Dronedarone (INN)
D02587  
Metildigoxin (JP16)
D02914  
Amlodipine maleate (USAN)
D03406  
Cariporide mesylate (USAN)
D03655  
Darodipine (USAN/INN)
D03830  
Diltiazem malate (USAN)
D03914  
Dronedarone hydrochloride (USAN)
D04510  
Imciromab pentetate (USAN)
D04657  
Lacidipine (USAN/INN)
D05442  
Perhexiline maleate (USAN)
D06881  
Acetyldigitoxin (INN)
D07147  
Gitoformate (INN)
D07450  
Amlodipine (INN)
D07494  
Barnidipine (INN)
D07509  
Benidipine (INN)
D07520  
Bepridil (INN)
D07555  
Acetyldigoxin
D07556  
beta-Acetyldigoxin
D07845  
Diltiazem (INN)
D07886  
Efonidipine (INN)
D08009  
Gallopamil (INN)
D08111  
Lercanidipine (INN)
D08155  
Manidipine (INN)
D08270  
Nicardipine (INN)
D08340  
Perhexiline (INN)
D08892  
Clevidipine (USAN/INN)
D09036  
Zoniporide mesylate (INN/USAN)
D09847  
Metildigoxin (INN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
775  
CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776  
CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
778  
CACNA1F; calcium channel, voltage-dependent, L type, alpha 1F subunit [KO:K04853]
779  
CACNA1S; calcium channel, voltage-dependent, L type, alpha 1S subunit [KO:K04857]
782  
CACNB1; calcium channel, voltage-dependent, beta 1 subunit [KO:K04862]
783  
CACNB2; calcium channel, voltage-dependent, beta 2 subunit [KO:K04863]
784  
CACNB3; calcium channel, voltage-dependent, beta 3 subunit [KO:K04864]
785  
CACNB4; calcium channel, voltage-dependent, beta 4 subunit [KO:K04865]
781  
CACNA2D1; calcium channel, voltage-dependent, alpha 2/delta subunit 1 [KO:K04858]
9254  
CACNA2D2; calcium channel, voltage-dependent, alpha 2/delta subunit 2 [KO:K04859]
55799  
CACNA2D3; calcium channel, voltage-dependent, alpha 2/delta subunit 3 [KO:K04860]
93589  
CACNA2D4; calcium channel, voltage-dependent, alpha 2/delta subunit 4 [KO:K04861]
786  
CACNG1; calcium channel, voltage-dependent, gamma subunit 1 [KO:K04866]
10369  
CACNG2; calcium channel, voltage-dependent, gamma subunit 2 [KO:K04867]
10368  
CACNG3; calcium channel, voltage-dependent, gamma subunit 3 [KO:K04868]
27092  
CACNG4; calcium channel, voltage-dependent, gamma subunit 4 [KO:K04869]
27091  
CACNG5; calcium channel, voltage-dependent, gamma subunit 5 [KO:K04870]
59285  
CACNG6; calcium channel, voltage-dependent, gamma subunit 6 [KO:K04871]
59284  
CACNG7; calcium channel, voltage-dependent, gamma subunit 7 [KO:K04872]
59283  
CACNG8; calcium channel, voltage-dependent, gamma subunit 8 [KO:K04873]
6262  
RYR2; ryanodine receptor 2 (cardiac) [KO:K04962]
7134  
TNNC1; troponin C type 1 (slow) [KO:K05865]
7137  
TNNI3; troponin I type 3 (cardiac) [KO:K12044]
7139  
TNNT2; troponin T type 2 (cardiac) [KO:K12045]
7168  
TPM1; tropomyosin 1 (alpha) [KO:K10373]
7169  
TPM2; tropomyosin 2 (beta) [KO:K10374]
7170  
TPM3; tropomyosin 3 [KO:K09290]
7171  
TPM4; tropomyosin 4 [KO:K10375]
70  
ACTC1; actin, alpha, cardiac muscle 1 [KO:K12314]
4634  
MYL3; myosin, light chain 3, alkali [KO:K12749]
4633  
MYL2; myosin, light chain 2, regulatory, cardiac, slow [KO:K10351]
7386  
UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
4519  
CYTB; cytochrome b [KO:K00412]
1537  
CYC1; cytochrome c-1 [KO:K00413]
7384  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
7385  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
7388  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
440567  
UQCRHL; ubiquinol-cytochrome c reductase hinge protein-like [KO:K00416]
7381  
UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
27089  
UQCRQ; ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa [KO:K00418]
29796  
UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
10975  
UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
4514  
COX3; cytochrome c oxidase III [KO:K02262]
4512  
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
4513  
COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  
COX4I2; cytochrome c oxidase subunit IV isoform 2 (lung) [KO:K02263]
1327  
COX4I1; cytochrome c oxidase subunit IV isoform 1 [KO:K02263]
9377  
COX5A; cytochrome c oxidase subunit Va [KO:K02264]
1329  
COX5B; cytochrome c oxidase subunit Vb [KO:K02265]
1337  
COX6A1; cytochrome c oxidase subunit VIa polypeptide 1 [KO:K02266]
1339  
COX6A2; cytochrome c oxidase subunit VIa polypeptide 2 [KO:K02266]
1340  
COX6B1; cytochrome c oxidase subunit VIb polypeptide 1 (ubiquitous) [KO:K02267]
125965  
COX6B2; cytochrome c oxidase subunit VIb polypeptide 2 (testis) [KO:K02267]
1345  
COX6C; cytochrome c oxidase subunit VIc [KO:K02268]
1346  
COX7A1; cytochrome c oxidase subunit VIIa polypeptide 1 (muscle) [KO:K02270]
1347  
COX7A2; cytochrome c oxidase subunit VIIa polypeptide 2 (liver) [KO:K02270]
9167  
COX7A2L; cytochrome c oxidase subunit VIIa polypeptide 2 like [KO:K02270]
1349  
COX7B; cytochrome c oxidase subunit VIIb [KO:K02271]
170712  
COX7B2; cytochrome c oxidase subunit VIIb2 [KO:K02271]
1350  
COX7C; cytochrome c oxidase subunit VIIc [KO:K02272]
341947  
COX8C; cytochrome c oxidase subunit VIIIC [KO:K02273]
1351  
COX8A; cytochrome c oxidase subunit VIIIA (ubiquitous) [KO:K02273]
476  
ATP1A1; ATPase, Na+/K+ transporting, alpha 1 polypeptide [KO:K01539] [EC:3.6.3.9]
477  
ATP1A2; ATPase, Na+/K+ transporting, alpha 2 polypeptide [KO:K01539] [EC:3.6.3.9]
478  
ATP1A3; ATPase, Na+/K+ transporting, alpha 3 polypeptide [KO:K01539] [EC:3.6.3.9]
480  
ATP1A4; ATPase, Na+/K+ transporting, alpha 4 polypeptide [KO:K01539] [EC:3.6.3.9]
23439  
ATP1B4; ATPase, Na+/K+ transporting, beta 4 polypeptide [KO:K01540]
481  
ATP1B1; ATPase, Na+/K+ transporting, beta 1 polypeptide [KO:K01540]
482  
ATP1B2; ATPase, Na+/K+ transporting, beta 2 polypeptide [KO:K01540]
483  
ATP1B3; ATPase, Na+/K+ transporting, beta 3 polypeptide [KO:K01540]
486  
FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
6548  
SLC9A1; solute carrier family 9, subfamily A (NHE1, cation proton antiporter 1), member 1 [KO:K05742]
10479  
SLC9A6; solute carrier family 9, subfamily A (NHE6, cation proton antiporter 6), member 6 [KO:K12041]
4624  
MYH6; myosin, heavy chain 6, cardiac muscle, alpha [KO:K10352]
4625  
MYH7; myosin, heavy chain 7, cardiac muscle, beta [KO:K10352]
488  
ATP2A2; ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 [KO:K05853] [EC:3.6.3.8]
6546  
SLC8A1; solute carrier family 8 (sodium/calcium exchanger), member 1 [KO:K05849]
Compound
C00076  
Calcium cation
C00080  
H+
C00238  
Potassium cation
C01330  
Sodium cation
Reference
  Authors
Bers DM
  Title
Calcium cycling and signaling in cardiac myocytes.
  Journal
Annu Rev Physiol 70:23-49 (2008)
Reference
  Authors
Bers DM
  Title
Cardiac excitation-contraction coupling.
  Journal
Nature 415:198-205 (2002)
Reference
  Authors
Endoh M
  Title
Signal transduction and Ca2+ signaling in intact myocardium.
  Journal
J Pharmacol Sci 100:525-37 (2006)
Reference
  Authors
Endoh M
  Title
Cardiac Ca2+ signaling and Ca2+ sensitizers.
  Journal
Circ J 72:1915-25 (2008)
Reference
  Authors
Bers DM, Despa S
  Title
Cardiac myocytes Ca2+ and Na+ regulation in normal and failing hearts.
  Journal
J Pharmacol Sci 100:315-22 (2006)
Reference
  Authors
Gordon AM, Homsher E, Regnier M
  Title
Regulation of contraction in striated muscle.
  Journal
Physiol Rev 80:853-924 (2000)
Reference
  Authors
Phrommintikul A, Chattipakorn N
  Title
Roles of cardiac ryanodine receptor in heart failure and sudden cardiac death.
  Journal
Int J Cardiol 112:142-52 (2006)
Reference
  Authors
Lacinova L
  Title
Voltage-dependent calcium channels.
  Journal
Gen Physiol Biophys 24 Suppl 1:1-78 (2005)
Reference
  Authors
Lingrel J, Moseley A, Dostanic I, Cougnon M, He S, James P, Woo A, O'Connor K, Neumann J
  Title
Functional roles of the alpha isoforms of the Na,K-ATPase.
  Journal
Ann N Y Acad Sci 986:354-9 (2003)
Reference
  Authors
Berg JS, Powell BC, Cheney RE
  Title
A millennial myosin census.
  Journal
Mol Biol Cell 12:780-94 (2001)
Reference
  Authors
Parmacek MS, Solaro RJ
  Title
Biology of the troponin complex in cardiac myocytes.
  Journal
Prog Cardiovasc Dis 47:159-76 (2004)
Reference
  Authors
Yamashita H, Sugiura S, Fujita H, Yasuda S, Nagai R, Saeki Y, Sunagawa K, Sugi H
  Title
Myosin light chain isoforms modify force-generating ability of cardiac myosin by changing the kinetics of actin-myosin interaction.
  Journal
Cardiovasc Res 60:580-8 (2003)
KO pathway
 
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