PathBank

Pathway Description

Muscle/Heart Contraction

Bos taurus

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

Katan M, Kriz RW, Totty N, Philp R, Meldrum E, Aldape RA, Knopf JL, Parker PJ: Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities. Cell. 1988 Jul 15;54(2):171-7. doi: 10.1016/0092-8674(88)90549-1.

Pubmed: 2455601

Ryu SH, Kim UH, Wahl MI, Brown AB, Carpenter G, Huang KP, Rhee SG: Feedback regulation of phospholipase C-beta by protein kinase C. J Biol Chem. 1990 Oct 15;265(29):17941-5.

Pubmed: 2211670

Sacchetto R, Bertipaglia I, Giannetti S, Cendron L, Mascarello F, Damiani E, Carafoli E, Zanotti G: Crystal structure of sarcoplasmic reticulum Ca2+-ATPase (SERCA) from bovine muscle. J Struct Biol. 2012 Apr;178(1):38-44. doi: 10.1016/j.jsb.2012.02.008. Epub 2012 Feb 24.

Pubmed: 22387132

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

Forsyth SE, Hoger A, Hoger JH: Molecular cloning and expression of a bovine endothelial inward rectifier potassium channel. FEBS Lett. 1997 Jun 9;409(2):277-82. doi: 10.1016/s0014-5793(97)00514-0.

Pubmed: 9202161

Yang D, Sun F, Thomas LL, Offord J, MacCallum DK, Dawson DC, Hughes BA, Ernst SA: Molecular cloning and expression of an inwardly rectifying K(+) channel from bovine corneal endothelial cells. Invest Ophthalmol Vis Sci. 2000 Sep;41(10):2936-44.

Pubmed: 10967048

Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.

Pubmed: 19393038

Garcia-Guzman M, Calvo S, Cena V, Criado M: Molecular cloning and permanent expression in a neuroblastoma cell line of a fast inactivating potassium channel from bovine adrenal medulla. FEBS Lett. 1992 Aug 24;308(3):283-9. doi: 10.1016/0014-5793(92)81294-v.

Pubmed: 1505668

Scott VE, Muniz ZM, Sewing S, Lichtinghagen R, Parcej DN, Pongs O, Dolly JO: Antibodies specific for distinct Kv subunits unveil a heterooligomeric basis for subtypes of alpha-dendrotoxin-sensitive K+ channels in bovine brain. Biochemistry. 1994 Feb 22;33(7):1617-23. doi: 10.1021/bi00173a001.

Pubmed: 8110763

Frings S, Brull N, Dzeja C, Angele A, Hagen V, Kaupp UB, Baumann A: Characterization of ether-a-go-go channels present in photoreceptors reveals similarity to IKx, a K+ current in rod inner segments. J Gen Physiol. 1998 Apr;111(4):583-99. doi: 10.1085/jgp.111.4.583.

Pubmed: 9524140

Taguchi Y, Saeki K, Komano T: Functional analysis of MRP1 cloned from bovine. FEBS Lett. 2002 Jun 19;521(1-3):211-3. doi: 10.1016/s0014-5793(02)02816-8.

Pubmed: 12067707

Weyand I, Godde M, Frings S, Weiner J, Muller F, Altenhofen W, Hatt H, Kaupp UB: Cloning and functional expression of a cyclic-nucleotide-gated channel from mammalian sperm. Nature. 1994 Apr 28;368(6474):859-63. doi: 10.1038/368859a0.

Pubmed: 7512693

Biel M, Zong X, Distler M, Bosse E, Klugbauer N, Murakami M, Flockerzi V, Hofmann F: Another member of the cyclic nucleotide-gated channel family, expressed in testis, kidney, and heart. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3505-9. doi: 10.1073/pnas.91.9.3505.

Pubmed: 8170936

Yoo SH, Oh YS, Kang MK, Huh YH, So SH, Park HS, Park HY: Localization of three types of the inositol 1,4,5-trisphosphate receptor/Ca(2+) channel in the secretory granules and coupling with the Ca(2+) storage proteins chromogranins A and B. J Biol Chem. 2001 Dec 7;276(49):45806-12. doi: 10.1074/jbc.M107532200. Epub 2001 Oct 2.

Pubmed: 11584008

Marks AR, Tempst P, Chadwick CC, Riviere L, Fleischer S, Nadal-Ginard B: Smooth muscle and brain inositol 1,4,5-trisphosphate receptors are structurally and functionally similar. J Biol Chem. 1990 Dec 5;265(34):20719-22.

Pubmed: 2174422

Schlossmann J, Ammendola A, Ashman K, Zong X, Huber A, Neubauer G, Wang GX, Allescher HD, Korth M, Wilm M, Hofmann F, Ruth P: Regulation of intracellular calcium by a signalling complex of IRAG, IP3 receptor and cGMP kinase Ibeta. Nature. 2000 Mar 9;404(6774):197-201. doi: 10.1038/35004606.

Pubmed: 10724174

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

Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.

Visualize Compound Data

		Adenosine diphosphate
		Adenosine triphosphate
		Calcium
		DG(14:0/14:1(9Z)/0:0)
		Inositol 1,4,5-trisphosphate
		Magnesium
		Phosphate
		PIP2(16:0/20:3(8Z,11Z,14Z))
		Potassium
		Sodium
		Water

Visualize Protein Data

		1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1
		Alpha-1-syntrophin
		ATP-sensitive inward rectifier potassium channel 12
		Beta-1 adrenergic receptor
		Calcium voltage-gated channel auxiliary subunit alpha2delta 2
		Calcium voltage-gated channel subunit alpha1 H
		Calmodulin
		cAMP-dependent protein kinase catalytic subunit alpha
		cAMP-dependent protein kinase type I-alpha regulatory subunit
		Cardiac phospholamban
		Cyclic nucleotide-gated cation channel alpha-3
		Dol-P-Glc:Glc(2)Man(9)GlcNAc(2)-PP-Dol alpha-1,2-glucosyltransferase
		G protein-activated inward rectifier potassium channel 1
		G protein-activated inward rectifier potassium channel 4
		Inositol 1,4,5-trisphosphate receptor type 1
		Inward rectifier potassium channel 2
		Kv channel-interacting protein 4
		MAGUK p55 subfamily member 7
		Multidrug resistance-associated protein 1
		Muscarinic acetylcholine receptor M2
		Myosin light chain kinase, smooth muscle
		Potassium channel subfamily K member 1
		Potassium voltage-gated channel subfamily A member 4
		Potassium voltage-gated channel subfamily D member 1
		Potassium voltage-gated channel subfamily E regulatory subunit 2
		Potassium voltage-gated channel subfamily H member 1
		Potassium voltage-gated channel subfamily KQT member 3
		Potassium voltage-gated channel, Isk-related family, member 1
		Sarcoplasmic/endoplasmic reticulum calcium ATPase 1
		Sodium channel protein
		Sodium/calcium exchanger 1
		Tropomyosin alpha-1 chain
		Tropomyosin beta chain
		Troponin C, slow skeletal and cardiac muscles
		Troponin I, cardiac muscle
		Troponin T, cardiac muscle
		Troponin T, fast skeletal muscle
		Troponin T, slow skeletal muscle
		Type-1 angiotensin II receptor
		Voltage-dependent L-type calcium channel subunit alpha
		Voltage-dependent L-type calcium channel subunit beta-1