Top ▲
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
The ryanodine receptors (RyRs) are found on intracellular Ca2+ storage/release organelles. The family of RyR genes encodes three highly related Ca2+ release channels: RyR1, RyR2 and RyR3, which assemble as large tetrameric structures. These RyR channels are ubiquitously expressed in many types of cells and participate in a variety of important Ca2+ signaling phenomena (neurotransmission, secretion, etc.). In addition to the three mammalian isoforms described below, various nonmammalian isoforms of the ryanodine receptor have been identified [4]. The function of the ryanodine receptor channels may also be influenced by closely associated proteins such as the tacrolimus (FK506)-binding protein, calmodulin [5], triadin, calsequestrin, junctin and sorcin, and by protein kinases and phosphatases. Recent studies solving the structure of the ryanodine receptor have shed light on the structural basis of ryanodine receptor function [see, for example, Samso (2017) [3] and Meissner (2017) [2]].
RyR1 C Show summary »« Hide summary More detailed page
|
||||||||||||||||||||||||||||||||||||||
RyR2 C Show summary »« Hide summary More detailed page
|
||||||||||||||||||||||||||||||||||||||
RyR3 C Show summary »« Hide summary More detailed page
|
* Key recommended reading is highlighted with an asterisk
Berridge MJ, Bootman MD, Roderick HL. (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol, 4 (7): 517-29. [PMID:12838335]
Berridge MJ, Lipp P, Bootman MD. (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol, 1 (1): 11-21. [PMID:11413485]
Betzenhauser MJ, Marks AR. (2010) Ryanodine receptor channelopathies. Pflugers Arch, 460 (2): 467-80. [PMID:20179962]
Bolton TB. (2006) Calcium events in smooth muscles and their interstitial cells; physiological roles of sparks. J Physiol (Lond.), 570 (Pt 1): 5-11. [PMID:16195319]
Bouchard R, Pattarini R, Geiger JD. (2003) Presence and functional significance of presynaptic ryanodine receptors. Prog Neurobiol, 69 (6): 391-418. [PMID:12880633]
Collin T, Marty A, Llano I. (2005) Presynaptic calcium stores and synaptic transmission. Curr Opin Neurobiol, 15 (3): 275-81. [PMID:15919193]
Dulhunty AF, Beard NA, Pouliquin P, Casarotto MG. (2007) Agonists and antagonists of the cardiac ryanodine receptor: potential therapeutic agents?. Pharmacol Ther, 113 (2): 247-63. [PMID:17055586]
* Dulhunty AF, Board PG, Beard NA, Casarotto MG. (2017) Physiology and Pharmacology of Ryanodine Receptor Calcium Release Channels. Adv Pharmacol, 79: 287-324. [PMID:28528672]
Eisner DA, Díaz ME, O'Neill SC, Trafford AW. (2004) Physiological and pathological modulation of ryanodine receptor function in cardiac muscle. Cell Calcium, 35 (6): 583-9. [PMID:15110148]
Endo M. (2009) Calcium-induced calcium release in skeletal muscle. Physiol Rev, 89 (4): 1153-76. [PMID:19789379]
Fill M, Copello JA. (2002) Ryanodine receptor calcium release channels. Physiol Rev, 82 (4): 893-922. [PMID:12270947]
Gaburjakova M, Bal NC, Gaburjakova J, Periasamy M. (2013) Functional interaction between calsequestrin and ryanodine receptor in the heart. Cell Mol Life Sci, 70 (16): 2935-45. [PMID:23109100]
Hamilton SL, Serysheva II. (2009) Ryanodine receptor structure: progress and challenges. J Biol Chem, 284 (7): 4047-51. [PMID:18927076]
Kushnir A, Betzenhauser MJ, Marks AR. (2010) Ryanodine receptor studies using genetically engineered mice. FEBS Lett, 584 (10): 1956-65. [PMID:20214899]
Kushnir A, Marks AR. (2010) The ryanodine receptor in cardiac physiology and disease. Adv Pharmacol, 59: 1-30. [PMID:20933197]
Lanner JT, Georgiou DK, Joshi AD, Hamilton SL. (2010) Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol, 2 (11): a003996. [PMID:20961976]
MacMillan D. (2013) FK506 binding proteins: cellular regulators of intracellular Ca2+ signalling. Eur J Pharmacol, 700 (1-3): 181-93. [PMID:23305836]
McCauley MD, Wehrens XH. (2011) Ryanodine receptor phosphorylation, calcium/calmodulin-dependent protein kinase II, and life-threatening ventricular arrhythmias. Trends Cardiovasc Med, 21 (2): 48-51. [PMID:22578240]
Meissner G. (2004) Molecular regulation of cardiac ryanodine receptor ion channel. Cell Calcium, 35 (6): 621-8. [PMID:15110152]
* Meissner G. (2017) The structural basis of ryanodine receptor ion channel function. J Gen Physiol, 149 (12): 1065-1089. [PMID:29122978]
Nahorski SR. (2006) Pharmacology of intracellular signalling pathways. Br J Pharmacol, 147 Suppl 1: S38-45. [PMID:16402119]
Niggli E, Ullrich ND, Gutierrez D, Kyrychenko S, Poláková E, Shirokova N. (2013) Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling. Biochim Biophys Acta, 1833 (4): 866-75. [PMID:22960642]
* O'Brien F, Venturi E, Sitsapesan R. (2015) The ryanodine receptor provides high throughput Ca2+-release but is precisely regulated by networks of associated proteins: a focus on proteins relevant to phosphorylation. Biochem Soc Trans, 43 (3): 426-33. [PMID:26009186]
Rossi D, Sorrentino V. (2002) Molecular genetics of ryanodine receptors Ca2+-release channels. Cell Calcium, 32 (5-6): 307-19. [PMID:12543091]
* Samsó M. (2017) A guide to the 3D structure of the ryanodine receptor type 1 by cryoEM. Protein Sci, 26 (1): 52-68. [PMID:27671094]
Shoshan-Barmatz V, Ashley RH. (1998) The structure, function, and cellular regulation of ryanodine-sensitive Ca2+ release channels. Int Rev Cytol, 183: 185-270. [PMID:9666568]
Sitsapesan R, Williams AJ. (1998) The Structure and Function of Ryanodine Receptors. In Edited by Sitsapesan, R, Williams, AJ. (Imperial College Press.) . [ISBN:9781860941450]
Sutko JL, Airey JA. (1996) Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity in function?. Physiol Rev, 76 (4): 1027-71. [PMID:8874493]
Sutko JL, Airey JA, Welch W, Ruest L. (1997) The pharmacology of ryanodine and related compounds. Pharmacol Rev, 49 (1): 53-98. [PMID:9085309]
Taur Y, Frishman WH. (2005) The cardiac ryanodine receptor (RyR2) and its role in heart disease. Cardiol Rev, 13 (3): 142-6. [PMID:15831148]
Van Petegem F. (2012) Ryanodine receptors: structure and function. J Biol Chem, 287 (38): 31624-32. [PMID:22822064]
* Van Petegem F. (2015) Ryanodine receptors: allosteric ion channel giants. J Mol Biol, 427 (1): 31-53. [PMID:25134758]
Verkhratsky A. (2005) Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol Rev, 85 (1): 201-79. [PMID:15618481]
* Zalk R, Marks AR. (2017) Ca2+ Release Channels Join the 'Resolution Revolution'. Trends Biochem Sci, 42 (7): 543-555. [PMID:28499500]
Zucchi R, Ronca-Testoni S. (1997) The sarcoplasmic reticulum Ca2+ channel/ryanodine receptor: modulation by endogenous effectors, drugs and disease states. Pharmacol Rev, 49 (1): 1-51. [PMID:9085308]
1. Gao L, Balshaw D, Xu L, Tripathy A, Xin C, Meissner G. (2000) Evidence for a role of the lumenal M3-M4 loop in skeletal muscle Ca(2+) release channel (ryanodine receptor) activity and conductance. Biophys J, 79 (2): 828-40. [PMID:10920015]
2. Meissner G. (2017) The structural basis of ryanodine receptor ion channel function. J Gen Physiol, 149 (12): 1065-1089. [PMID:29122978]
3. Samsó M. (2017) A guide to the 3D structure of the ryanodine receptor type 1 by cryoEM. Protein Sci, 26 (1): 52-68. [PMID:27671094]
4. Sutko JL, Airey JA. (1996) Ryanodine receptor Ca2+ release channels: does diversity in form equal diversity in function?. Physiol Rev, 76 (4): 1027-71. [PMID:8874493]
5. Yamaguchi N, Xu L, Pasek DA, Evans KE, Meissner G. (2003) Molecular basis of calmodulin binding to cardiac muscle Ca(2+) release channel (ryanodine receptor). J Biol Chem, 278 (26): 23480-6. [PMID:12707260]
6. Zhao M, Li P, Li X, Zhang L, Winkfein RJ, Chen SR. (1999) Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem, 274 (37): 25971-4. [PMID:10473538]
Database page citation:
Ryanodine receptors (RyR). Accessed on 14/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=125.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License
The modulators of channel function included in this table are those most commonly used to identify ryanodine-sensitive Ca2+ release pathways. Numerous other modulators of ryanodine receptor/channel function can be found in the reviews listed below. The absence of a modulator of a particular isoform of receptor indicates that the action of that modulator has not been determined, not that it is without effect. The potential role of cyclic ADP ribose as an endogenous regulator of ryanodine receptor channels is controversial. A region of RyR likely to be involved in ion translocation and selection has been identified [1,6].