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Pathway Description
Muscle/Heart Contraction
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Physiological
Created: 2018-09-10
Last Updated: 2019-09-13
Tubular striated muscle cells (i.e. skeletal and cardiac myocytes) are composed of bundles of rod-like myofibrils. Each individual myofibril consists of many repeating units called sarcomeres. These functional units, in turn, are composed of many alternating actin and mysoin protein filaments that produce muscle contraction. The muscle contraction process is initiated when the muscle cell is depolarized enough for an action potential to occur. When acetylcholine is released from the motor neuron axon terminals that are adjacent to the muscle cells, it binds to receptors on the sarcolemma (muscle cell membrane), causing nicotinic acetylcholine receptors to be activated and the sodium/potassium channels to be opened. The fast influx of sodium and slow efflux of potassium through the channel causes depolarization. The resulting action potential that is generated travels along the sarcolemma and down the T-tubule, activating the L-type voltage-dependent calcium channels on the sarcolemma and ryanodine receptors on the sarcoplasmic reticulum. When these are activated, it triggers the release of calcium ions from the sarcoplasmic reticulum into the cytosol. From there, the calcium ions bind to the protein troponin which displaces the tropomysoin filaments from the binding sites on the actin filaments. This allows for myosin filaments to be able to bind to the actin. According to the Sliding Filament Theory, the myosin heads that have an ADP and phosphate attached binds to the actin, forming a cross-bridge. Once attached, the myosin performs a powerstroke which slides the actin filaments together. The ATP and phosphate are dislodged during this process. However, ATP now binds to the myosin head, which causes the myosin to detach from the actin. The cycle repeats once the attached ATP dissociates into ADP and phosphate, and the myosin performs another powerstroke, bringing the actin filaments even closer together. Numerous actin filaments being pulled together simultaneously across many muscles cells triggers muscle contraction.
References
Muscle/Heart Contraction References
Ehringer MA, Thompson J, Conroy O, Xu Y, Yang F, Canniff J, Beeson M, Gordon L, Bennett B, Johnson TE, Sikela JM: High-throughput sequence identification of gene coding variants within alcohol-related QTLs. Mamm Genome. 2001 Aug;12(8):657-63.
Pubmed: 11471062
Church DM, Goodstadt L, Hillier LW, Zody MC, Goldstein S, She X, Bult CJ, Agarwala R, Cherry JL, DiCuccio M, Hlavina W, Kapustin Y, Meric P, Maglott D, Birtle Z, Marques AC, Graves T, Zhou S, Teague B, Potamousis K, Churas C, Place M, Herschleb J, Runnheim R, Forrest D, Amos-Landgraf J, Schwartz DC, Cheng Z, Lindblad-Toh K, Eichler EE, Ponting CP: Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5;7(5):e1000112. doi: 10.1371/journal.pbio.1000112. Epub 2009 May 26.
Pubmed: 19468303
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
Ver Heyen M, Reed TD, Blough RI, Baker DL, Zilberman A, Loukianov E, Van Baelen K, Raeymaekers L, Periasamy M, Wuytack F: Structure and organization of the mouse Atp2a2 gene encoding the sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) isoforms. Mamm Genome. 2000 Feb;11(2):159-63.
Pubmed: 10656932
Stefanovic B, Stefanovic L, Schnabl B, Bataller R, Brenner DA: TRAM2 protein interacts with endoplasmic reticulum Ca2+ pump Serca2b and is necessary for collagen type I synthesis. Mol Cell Biol. 2004 Feb;24(4):1758-68. doi: 10.1128/mcb.24.4.1758-1768.2004.
Pubmed: 14749390
Kubo Y, Baldwin TJ, Jan YN, Jan LY: Primary structure and functional expression of a mouse inward rectifier potassium channel. Nature. 1993 Mar 11;362(6416):127-33. doi: 10.1038/362127a0.
Pubmed: 7680768
Morishige K, Takahashi N, Findlay I, Koyama H, Zanelli JS, Peterson C, Jenkins NA, Copeland NG, Mori N, Kurachi Y: Molecular cloning, functional expression and localization of an inward rectifier potassium channel in the mouse brain. FEBS Lett. 1993 Dec 28;336(3):375-80. doi: 10.1016/0014-5793(93)80840-q.
Pubmed: 8282096
Rae JL, Shepard AR: Inwardly rectifying potassium channels in lens epithelium are from the IRK1 (Kir 2.1) family. Exp Eye Res. 1998 Mar;66(3):347-59. doi: 10.1006/exer.1997.0432.
Pubmed: 9533862
Morishige K, Takahashi N, Jahangir A, Yamada M, Koyama H, Zanelli JS, Kurachi Y: Molecular cloning and functional expression of a novel brain-specific inward rectifier potassium channel. FEBS Lett. 1994 Jun 13;346(2-3):251-6. doi: 10.1016/0014-5793(94)00483-8.
Pubmed: 8013643
Lesage F, Duprat F, Fink M, Guillemare E, Coppola T, Lazdunski M, Hugnot JP: Cloning provides evidence for a family of inward rectifier and G-protein coupled K+ channels in the brain. FEBS Lett. 1994 Oct 10;353(1):37-42. doi: 10.1016/0014-5793(94)01007-2.
Pubmed: 7926018
Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y: Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses. Am J Physiol Cell Physiol. 2002 Jun;282(6):C1396-403. doi: 10.1152/ajpcell.00615.2001.
Pubmed: 11997254
Kobayashi T, Ikeda K, Ichikawa T, Abe S, Togashi S, Kumanishi T: Molecular cloning of a mouse G-protein-activated K+ channel (mGIRK1) and distinct distributions of three GIRK (GIRK1, 2 and 3) mRNAs in mouse brain. Biochem Biophys Res Commun. 1995 Mar 28;208(3):1166-73. doi: 10.1006/bbrc.1995.1456.
Pubmed: 7702616
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Nishida M, MacKinnon R: Structural basis of inward rectification: cytoplasmic pore of the G protein-gated inward rectifier GIRK1 at 1.8 A resolution. Cell. 2002 Dec 27;111(7):957-65. doi: 10.1016/s0092-8674(02)01227-8.
Pubmed: 12507423
Lesage F, Guillemare E, Fink M, Duprat F, Heurteaux C, Fosset M, Romey G, Barhanin J, Lazdunski M: Molecular properties of neuronal G-protein-activated inwardly rectifying K+ channels. J Biol Chem. 1995 Dec 1;270(48):28660-7. doi: 10.1074/jbc.270.48.28660.
Pubmed: 7499385
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. doi: 10.1126/science.1112014.
Pubmed: 16141072
Liss B, Franz O, Sewing S, Bruns R, Neuhoff H, Roeper J: Tuning pacemaker frequency of individual dopaminergic neurons by Kv4.3L and KChip3.1 transcription. EMBO J. 2001 Oct 15;20(20):5715-24. doi: 10.1093/emboj/20.20.5715.
Pubmed: 11598014
Guo W, Li H, Aimond F, Johns DC, Rhodes KJ, Trimmer JS, Nerbonne JM: Role of heteromultimers in the generation of myocardial transient outward K+ currents. Circ Res. 2002 Mar 22;90(5):586-93. doi: 10.1161/01.res.0000012664.05949.e0.
Pubmed: 11909823
Kuo HC, Cheng CF, Clark RB, Lin JJ, Lin JL, Hoshijima M, Nguyen-Tran VT, Gu Y, Ikeda Y, Chu PH, Ross J, Giles WR, Chien KR: A defect in the Kv channel-interacting protein 2 (KChIP2) gene leads to a complete loss of I(to) and confers susceptibility to ventricular tachycardia. Cell. 2001 Dec 14;107(6):801-13. doi: 10.1016/s0092-8674(01)00588-8.
Pubmed: 11747815
Ohya S, Morohashi Y, Muraki K, Tomita T, Watanabe M, Iwatsubo T, Imaizumi Y: Molecular cloning and expression of the novel splice variants of K(+) channel-interacting protein 2. Biochem Biophys Res Commun. 2001 Mar 23;282(1):96-102. doi: 10.1006/bbrc.2001.4558.
Pubmed: 11263977
Attali B, Lesage F, Ziliani P, Guillemare E, Honore E, Waldmann R, Hugnot JP, Mattei MG, Lazdunski M, Barhanin J: Multiple mRNA isoforms encoding the mouse cardiac Kv1-5 delayed rectifier K+ channel. J Biol Chem. 1993 Nov 15;268(32):24283-9.
Pubmed: 8226976
London B, Guo W, Pan Xh, Lee JS, Shusterman V, Rocco CJ, Logothetis DA, Nerbonne JM, Hill JA: Targeted replacement of KV1.5 in the mouse leads to loss of the 4-aminopyridine-sensitive component of I(K,slow) and resistance to drug-induced qt prolongation. Circ Res. 2001 May 11;88(9):940-6. doi: 10.1161/hh0901.090929.
Pubmed: 11349004
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000588
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