KEGG   PATHWAY: hsa04260
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
Pathway map
hsa04260  Cardiac muscle contraction
hsa04260

Drug
D00112  G-Strophanthin (JAN)
D00297  Digitoxin (JAN/USP/INN)
D00298  Digoxin (JP18/USP)
D00319  Felodipine (JP18/USP/INN)
D00349  Isradipine (USP/INN)
D00437  Nifedipine (JP18/USP/INN)
D00438  Nimodipine (USP/INN)
D00615  Amlodipine besylate (USP)
D00616  Diltiazem hydrochloride (JP18/USP)
D00617  Nicardipine hydrochloride (JP18/USAN)
D00618  Nisoldipine (JAN/USAN/INN)
D00619  Verapamil hydrochloride (JP18/USP)
D00629  Nitrendipine (JP18/USAN/INN)
D00631  Bepridil hydrochloride (USAN)
D00645  Bretylium tosylate (USP)
D01104  Barnidipine hydrochloride (JAN)
D01145  Azelnidipine (JP18/INN)
D01151  Lemildipine (JAN/INN)
D01171  Monatepil maleate (JAN/USAN)
D01173  Cilnidipine (JP18/INN)
D01240  Deslanoside (JP18/USP/INN)
D01369  Bevantolol hydrochloride (JAN/USAN)
D01379  Proscillaridin (JAN/USAN/INN)
D01553  Manidipine hydrochloride (JP18)
D01562  Aranidipine (JAN/INN)
D01604  Efonidipine hydrochloride ethanolate (JAN)
D01849  Lercanidipine hydrochloride (JAN/USAN)
D01908  Nilvadipine (JP18/USAN/INN)
D01933  Vatanidipine hydrochloride (JAN)
D01969  Gallopamil hydrochloride (JAN)
D01972  Lanatoside C (JAN/INN)
D02045  Benidipine hydrochloride (JP18)
D02356  Verapamil (USAN/INN)
D02537  Dronedarone (INN)
D02587  Metildigoxin (JP18)
D02914  Amlodipine maleate (USAN)
D03067  Belfosdil (USAN/INN)
D03406  Cariporide mesylate (USAN)
D03536  Clentiazem maleate (JAN/USAN)
D03655  Darodipine (USAN/INN)
D03830  Diltiazem malate (USAN)
D03914  Dronedarone hydrochloride (USP)
D04193  Flordipine (USAN/INN)
D04510  Imciromab pentetate (USAN)
D04657  Lacidipine (USAN/INN)
D05024  Mibefradil dihydrochloride (USAN)
D05442  Perhexiline maleate (USAN)
D06129  Tiapamil hydrochloride (USAN)
D06881  Acetyldigitoxin (INN)
D07147  Gitoformate (INN)
D07185  Fendiline (INN)
D07450  Amlodipine (USP/INN)
D07494  Barnidipine (INN)
D07509  Benidipine (INN)
D07520  Bepridil (INN)
D07555  Acetyldigoxin
D07556  beta-Acetyldigoxin
D07845  Diltiazem (INN)
D07886  Efonidipine (INN)
D07943  Fendiline hydrochloride
D08009  Gallopamil (INN)
D08111  Lercanidipine (INN)
D08155  Manidipine (INN)
D08217  Mibefradil (INN)
D08270  Nicardipine (INN)
D08340  Perhexiline (INN)
D08892  Clevidipine (USAN/INN)
D08941  Levamlodipine malate (USAN)
D09036  Zoniporide mesylate (INN/USAN)
D09789  Kirenidipine hydrochloride (JAN)
D09833  Levosemotiadil fumarate (JAN)
D09847  Metildigoxin (INN)
D10932  Etripamil (USAN/INN)
D11723  Levamlodipine maleate (USAN)
D11881  Amlodipine benzoate
D12253  Aficamten (USAN/INN)
D12265  Mavacamten (JAN/USAN/INN)
D12804  Nelutroctiv (USAN/INN)
D12949  Delocamten (USAN)
Other DBs
GO: 0060048
Organism
Homo sapiens (human) [GN:hsa]
Gene
775  CACNA1C; calcium voltage-gated channel subunit alpha1 C [KO:K04850]
776  CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851]
778  CACNA1F; calcium voltage-gated channel subunit alpha1 F [KO:K04853]
779  CACNA1S; calcium voltage-gated channel subunit alpha1 S [KO:K04857]
782  CACNB1; calcium voltage-gated channel auxiliary subunit beta 1 [KO:K04862]
783  CACNB2; calcium voltage-gated channel auxiliary subunit beta 2 [KO:K04863]
784  CACNB3; calcium voltage-gated channel auxiliary subunit beta 3 [KO:K04864]
785  CACNB4; calcium voltage-gated channel auxiliary subunit beta 4 [KO:K04865]
781  CACNA2D1; calcium voltage-gated channel auxiliary subunit alpha2delta 1 [KO:K04858]
9254  CACNA2D2; calcium voltage-gated channel auxiliary subunit alpha2delta 2 [KO:K04859]
55799  CACNA2D3; calcium voltage-gated channel auxiliary subunit alpha2delta 3 [KO:K04860]
93589  CACNA2D4; calcium voltage-gated channel auxiliary subunit alpha2delta 4 [KO:K04861]
786  CACNG1; calcium voltage-gated channel auxiliary subunit gamma 1 [KO:K04866]
10369  CACNG2; calcium voltage-gated channel auxiliary subunit gamma 2 [KO:K04867]
10368  CACNG3; calcium voltage-gated channel auxiliary subunit gamma 3 [KO:K04868]
27092  CACNG4; calcium voltage-gated channel auxiliary subunit gamma 4 [KO:K04869]
27091  CACNG5; calcium voltage-gated channel auxiliary subunit gamma 5 [KO:K04870]
59285  CACNG6; calcium voltage-gated channel auxiliary subunit gamma 6 [KO:K04871]
59284  CACNG7; calcium voltage-gated channel auxiliary subunit gamma 7 [KO:K04872]
59283  CACNG8; calcium voltage-gated channel auxiliary subunit gamma 8 [KO:K04873]
6262  RYR2; ryanodine receptor 2 [KO:K04962]
444  ASPH; aspartate beta-hydroxylase [KO:K00476] [EC:1.14.11.16]
845  CASQ2; calsequestrin 2 [KO:K23445]
10345  TRDN; triadin [KO:K23449]
3270  HRC; histidine rich calcium binding protein [KO:K23450]
487  ATP2A1; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [KO:K05853] [EC:7.2.2.10]
489  ATP2A3; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 3 [KO:K05853] [EC:7.2.2.10]
488  ATP2A2; ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 [KO:K05853] [EC:7.2.2.10]
7134  TNNC1; troponin C1, slow skeletal and cardiac type [KO:K05865]
7137  TNNI3; troponin I3, cardiac type [KO:K12044]
7139  TNNT2; troponin T2, cardiac type [KO:K12045]
7168  TPM1; tropomyosin 1 [KO:K10373]
7169  TPM2; tropomyosin 2 [KO:K10374]
7170  TPM3; tropomyosin 3 [KO:K09290]
7171  TPM4; tropomyosin 4 [KO:K10375]
70  ACTC1; actin alpha cardiac muscle 1 [KO:K12314]
4625  MYH7; myosin heavy chain 7 [KO:K17751]
4624  MYH6; myosin heavy chain 6 [KO:K17751]
4633  MYL2; myosin light chain 2 [KO:K10351]
4634  MYL3; myosin light chain 3 [KO:K12749]
4635  MYL4; myosin light chain 4 [KO:K12750]
7386  UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:7.1.1.8]
4519  CYTB; cytochrome b [KO:K00412]
1537  CYC1; cytochrome c1 [KO:K00413]
7384  UQCRC1; ubiquinol-cytochrome c reductase core protein 1 [KO:K00414]
7385  UQCRC2; ubiquinol-cytochrome c reductase core protein 2 [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 [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 subunit III [KO:K02262]
4512  COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:7.1.1.9]
4513  COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263]
1327  COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263]
9377  COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
1329  COX5B; cytochrome c oxidase subunit 5B [KO:K02265]
1337  COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266]
1339  COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266]
1340  COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
125965  COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
1345  COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270]
1347  COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270]
9167  COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270]
1349  COX7B; cytochrome c oxidase subunit 7B [KO:K02271]
170712  COX7B2; cytochrome c oxidase subunit 7B2 [KO:K02271]
1350  COX7C; cytochrome c oxidase subunit 7C [KO:K02272]
341947  COX8C; cytochrome c oxidase subunit 8C [KO:K02273]
1351  COX8A; cytochrome c oxidase subunit 8A [KO:K02273]
6546  SLC8A1; solute carrier family 8 member A1 [KO:K05849]
6543  SLC8A2; solute carrier family 8 member A2 [KO:K05849]
6547  SLC8A3; solute carrier family 8 member A3 [KO:K05849]
10479  SLC9A6; solute carrier family 9 member A6 [KO:K12041]
84679  SLC9A7; solute carrier family 9 member A7 [KO:K12041]
476  ATP1A1; ATPase Na+/K+ transporting subunit alpha 1 [KO:K01539] [EC:7.2.2.13]
477  ATP1A2; ATPase Na+/K+ transporting subunit alpha 2 [KO:K01539] [EC:7.2.2.13]
478  ATP1A3; ATPase Na+/K+ transporting subunit alpha 3 [KO:K01539] [EC:7.2.2.13]
480  ATP1A4; ATPase Na+/K+ transporting subunit alpha 4 [KO:K01539] [EC:7.2.2.13]
23439  ATP1B4; ATPase Na+/K+ transporting family member beta 4 [KO:K01540]
481  ATP1B1; ATPase Na+/K+ transporting subunit beta 1 [KO:K01540]
482  ATP1B2; ATPase Na+/K+ transporting subunit beta 2 [KO:K01540]
483  ATP1B3; ATPase Na+/K+ transporting subunit beta 3 [KO:K01540]
486  FXYD2; FXYD domain containing ion transport regulator 2 [KO:K01538]
6548  SLC9A1; solute carrier family 9 member A1 [KO:K05742]
Compound
C00076  Calcium cation
C00080  H+
C00238  Potassium cation
C01330  Sodium cation
Reference
PMID:17988210
  Authors
Bers DM
  Title
Calcium cycling and signaling in cardiac myocytes.
  Journal
Annu Rev Physiol 70:23-49 (2008)
DOI:10.1146/annurev.physiol.70.113006.100455
Reference
PMID:11805843
  Authors
Bers DM
  Title
Cardiac excitation-contraction coupling.
  Journal
Nature 415:198-205 (2002)
DOI:10.1038/415198a
Reference
PMID:16799263
  Authors
Endoh M
  Title
Signal transduction and Ca2+ signaling in intact myocardium.
  Journal
J Pharmacol Sci 100:525-37 (2006)
DOI:10.1254/jphs.CPJ06009X
Reference
PMID:18981594
  Authors
Endoh M
  Title
Cardiac Ca2+ signaling and Ca2+ sensitizers.
  Journal
Circ J 72:1915-25 (2008)
DOI:10.1253/circj.CJ-08-0838
Reference
PMID:16552170
  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)
DOI:10.1254/jphs.CPJ06001X
Reference
PMID:10747208
  Authors
Gordon AM, Homsher E, Regnier M
  Title
Regulation of contraction in striated muscle.
  Journal
Physiol Rev 80:853-924 (2000)
DOI:10.1152/physrev.2000.80.2.853
Reference
PMID:16701909
  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)
DOI:10.1016/j.ijcard.2005.11.106
Reference
PMID:16096350
  Authors
Lacinova L
  Title
Voltage-dependent calcium channels.
  Journal
Gen Physiol Biophys 24 Suppl 1:1-78 (2005)
Reference
PMID:12763850
  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)
DOI:10.1111/j.1749-6632.2003.tb07214.x
Reference
PMID:11294886
  Authors
Berg JS, Powell BC, Cheney RE
  Title
A millennial myosin census.
  Journal
Mol Biol Cell 12:780-94 (2001)
DOI:10.1091/mbc.12.4.780
Reference
PMID:15736582
  Authors
Parmacek MS, Solaro RJ
  Title
Biology of the troponin complex in cardiac myocytes.
  Journal
Prog Cardiovasc Dis 47:159-76 (2004)
DOI:10.1016/j.pcad.2004.07.003
Reference
PMID:14659803
  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)
DOI:10.1016/j.cardiores.2003.09.011
Reference
PMID:19403607
  Authors
Pritchard TJ, Kranias EG
  Title
Junctin and the histidine-rich Ca2+ binding protein: potential roles in heart failure and arrhythmogenesis.
  Journal
J Physiol 587:3125-33 (2009)
DOI:10.1113/jphysiol.2009.172171
Reference
PMID:28596175
  Authors
Landstrom AP, Dobrev D, Wehrens XHT
  Title
Calcium Signaling and Cardiac Arrhythmias.
  Journal
Circ Res 120:1969-1993 (2017)
DOI:10.1161/CIRCRESAHA.117.310083
Related
pathway
hsa04020  Calcium signaling pathway
KO pathway
ko04260   
LinkDB

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