Ryanodine receptors channels

Sitsapesan R, Williams AJ 2000 Do inactivation mechanisms rather than adaptation hold the key to understanding ryanodine receptor channel gating J Gen Physiol 116 867-872 Somlyo AP 1985 Excitation-contraction coupling and the ultrastructure of smooth muscle. Circ Res 57 497-507... 

Kannan MS, Prakash YS, Brenner T, Mickelson JR, Sieck GC 1997 Role of ryanodine receptor channels in Ca2+ oscillations of porcine tracheal smooth muscle. Am J Physiol 272 L659-L664 Kirber MT, Walsh JVJ, Singer JJ 1988 Stretch-activated ion channels in smooth muscle a mechanism for the initiation of stretch-induced contraction. Pfliig Arch Eur J Physiol 412 339-345... 

Day, T.A., Haithcock, J., Kimber, M. and Maule, A.G. (2000) Functional ryanodine receptor channels in flat-worm muscle fibres. Parasitology 120, 417 122. 

Dantrolene is a hydantoin derivative related to phenytoin that has a unique mechanism of spasmolytic activity. In contrast to the centrally active drugs, dantrolene reduces skeletal muscle strength by interfering with excitation-contraction coupling in the muscle fibers. The normal contractile response involves release of calcium from its stores in the sarcoplasmic reticulum (see Figures 13-1 and 27-10). This activator calcium brings about the tension-generating interaction of actin with myosin. Calcium is released from the sarcoplasmic reticulum via a calcium channel, sometimes called the ryanodine receptor channel because the plant alkaloid ryanodine combines with a receptor on the channel protein and, in the case of the skeletal muscle channel, locks it in the open position. 

Velez P, Gyorke S, Escobar AL, Vergara J, Fill M. Adaptation of single cardiac ryanodine receptor channels. Biophys J 1997 72 691-7. 

Bull R, Marengo JJ, Finkelstein JP, Behrens MI, Alvarez O. 2003. SH oxidation coordinates subunits of rat brain ryanodine receptor channels activated by calcium and ATP. Am J Physiol Cell Physiol 285 Cl 19-028. 

Other drugs affect intracellular calcium channels of the endoplasmic or sarcoplasmic reticulum, e.g. inositol triphosphate receptor channels open in response to InsPs itself and certain other inositol phosphates, are sensitized by thiomersal (which increases the sensitivity of the receptor to InsPs by acting as a sulphydryl reagent) and antagonized by heparin. The various ryanodine receptor channels, at which a putative natural agonist is cyclic adenosine diphosphate ribose (cADP-R), are activated by caffeine and low concentrations of ryanodine (but antagonized by high concentrations of ryanodine and ruthenium red). 

Tinker A, Williams AJ. 1992. Divalent cation conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum. J Gen Physiol 100 479-493. 

Euden J, Mason SA, Viero C, Thomas NL, Williams AJ (2013) Investigations of the contribution of a putative glycine hinge to ryanodine receptor channel gating. J Biol Chem 288 16671-16679... 

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

A regenerative process whereby an intracellular Ca2+ channel (IP3 receptor or Ryanodine receptor) is itself stimulated by Ca2+, allowing thereby Ca2+ to promote its own release from intracellular stores. 

IP3 Receptor Ryanodine Receptor Non-selective Cations Channels TRP Channels... 

Inwardly Rectifying K+ Channels ATP-dependent K+ Channels Voltage-dependent Ca2+ Channels Ryanodine Receptor Voltage-dependent Na2+ Channels... 

Voltage-dependent Ca2+ Channels Ca2+ Channel Blockers Ryanodine Receptor... 

Ryanodine receptor (RyR) is an intracellular Ca2+ release channel in the sarcoplasmic reticulum (SR) or the endoplasmic reticulum (ER). RyR binds ryanodine (a plant alkaloid, see Drugs) with a high affinity, after which it is named. 

Fill M, Copello JA (2002) Ryanodine receptor calcium release channels. Physiol Rev 82 893-922... 

Franzini-Armstrong C, Protasi F (1997) Ryanodine receptor of striated muscles a complex channel capable of multiple interactions. Physiol Rev 77 699-672... 

S100A1 is the most abundant in the myocardium but is also expressed in brain and other tissues. S100A1 was found to stimulate Ca2+-induced Ca2+-release (CICR) in skeletal muscle terminal cisternae. In the presence of nanomolar Ca2+-concentrations, S100A1 binds to the ryanodine receptor increasing its channel open probability, and was shown to enhance SR Ca2+-release and contractile performance. Several animal models (over expressing S100A1 or S100A1-deficient mice) have... 

Sarcoplasmic reticulum (SR) is a form of the smoothfaced endoplasmic reticulum (ER) in muscles. It functions as an intracellular Ca2+ store for muscle contraction. Ca2+ is energetically sequestered into the SR by Ca2+-pump/sarcoplasmic endoplasmic reticulum Ca2+-ATPase (SERCA) and released via Ca2+ release channels on stimuli (ryanodine receptor in striated muscles and inositol 1,4,5-trisphosphate receptor in most smooth muscles). Endoplasmic reticulum in non-muscle tissues also functions as an intracellular Ca2+ store. 

Harioka, T., Sone, T., Toda, H. (1990). Ca release channel (ryanodine receptor) of skeletal muscle sarcoplasmic reticulum. J. Biol. Chem. 265, 2244-2256. 

Meissner, G. (1994). Ryanodine receptor/Ca release channels and their regulation by endogenous effectors. Ann. Rev. Physiol. 56,485-508. 

The Ca release channel is also known as the ryanodine receptor (RYR). There are two isoforms of this... 

Figure 49-8. Diagram of the relationships among the sarcolemma (plasma membrane), a T tubule, and two cisternae of the sarcoplasmic reticulum of skeletal muscle (not to scale). The T tubule extends inward from the sarcolemma. A wave of depolarization, initiated by a nerve impulse, is transmitted from the sarcolemma down the T tubule. It is then conveyed to the Ca release channel (ryanodine receptor), perhaps by interaction between it and the dihydropyridine receptor (slow Ca voltage channel), which are shown in close proximity. Release of Ca from the Ca release channel into the cytosol initiates contraction. Subsequently, Ca is pumped back into the cisternae of the sarcoplasmic reticulum by the Ca ATPase (Ca pump) and stored there, in part bound to calsequestrin.

Figure 49-9. Possible chain of events leading to opening of the Ca release channel. As indicated in the text, the Ca voltage channel and the Ca release channel have been shown to interact with each other in vitro via specific regions in their polypeptide chains. (DHPR, dihydropyridine receptor RYR1, ryanodine receptor 1.)...

Ca " " release channel (ryanodine receptor) in the sarcoplasmic reticulum [mutations] (MIM 180901) Malignant hyperthermia (MIM 145600) following administration of certain anesthetics (eg, halothane)... 

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