Sarcoplasmic reticulum, calcium release from

The ryanodine receptors are calcium release channels found in the endoplasmic reticulum and sarcoplasmic reticulum of muscle cells. One type of receptor can be activated by a depolarization signal (depolarization-induced calcium release). Another receptor type is activated by calcium ions (calcium-induced calcium release). The proteins received their name because they bind ryanodine, a toxin obtained from the stem and roots of the plant Ryania speciosa. Ryanodine inhibits sarcoplasmic reticulum calcium release, and acts as a paralytic agent. It was first used commercially in insecticides. 

Fig. 47.3. Events leading to sarcoplasmic reticulum calcium release in skeletal muscle. 1. Acetylcholine, released at the synaptic cleft, binds to acetylcholine receptors on the sar-colemma, leading to a change of conformation of the receptors such that they now act as an ion pore. This allows sodium to enter the cell and potassium to leave. 2. The membrane polarization that results from these ion movements is transmitted throughout the muscle fiber by the T-tubule system. 3. A receptor in the T-tubules (the dihydropyridine receptor, DHPR) is activated by membrane polarization (a voltage-gated activation) such that activated DHPR physically binds to and activates the ryanodine receptor in the sarcoplasmic reticulum (depolarization-induced calcium release). 4. The activation of the ryanodine receptor, which is a calcium channel, leads to calcium release from the SR into the sarcoplasm. In cardiac muscle, activation of DHPR leads to calcium release from the T-tubules, and this small calcium release is responsible for the activation of the cardiac ryanodine receptor (calcium-induced calcium release) to release large amounts of calcium into the sarcoplasm.

Shattock, M.J., Matsuura, H. and Hearse, D.J. (1991). Functional and electrophysiolc cal effects of oxidant stress on isolated ventricular muscle role for oscillatory calcium release from sarcoplasmic reticulum in arrhythmogenesis. Cardiovasc. Res. 25, 645-651. 

Trimm, J.L., Salama, G. and Abramson, J.J. (1986). Sulphydryl oxidation induces rapid calcium release from sarcoplasmic reticulum vesicles. J. Biol. Chem. 261, 16092-16098. 

For over three decades, laboratory research has shown caffeine to be effective at mobilizing calcium in skeletal muscle. In vitro experiments have amply demonstrated that caffeine lowers the excitability threshold and extends the length of muscular contractions via calcium release from the sarcoplasmic reticulum.1012 Caffeine also inhibits calcium reuptake by the sarcoplasmic reticulum, perpetuating calcium availability for muscle work.1318 Also, caffeine promotes increased twitch tension development in muscles.1718... 

Endo, M., Calcium release from the sarcoplasmic reticulum, Physiology Review, 57, 71, 1977. 

Fabiato, A. and Fabiato, F., Calcium release from sarcoplasmic reticulum, Circ Research, 40, 119, 1977. 

The first molecule, the Ca2+ channel, is required for coupling at the triad. Skeletal muscle contains higher concentrations of this L-type Ca2+ channel that can be accounted for on the basis of measured voltage-dependent Ca2+ influx because much of the Ca2+ channel protein in the T-tubular membrane does not actively gate calcium ion movement but, rather, acts as a voltage transducer that links depolarization of the T-tubular membrane to Ca2+ release through a receptor protein in the SR membrane. The ryanodine receptor mediates sarcoplasmic reticulum Ca2+ release. The bar-like structures that connect the terminal elements of the SR with the T-tubular membrane in the triad are formed by a large protein that is the principal pathway for Ca2+ release from the SR. This protein, which binds the... 

Missiaen L, Taylor CW, Berridge MJ 1992 Luminal Ca2+ promoting spontaneous Ca2+ release from inositol trisphosphate-sensitive stores in rat hepatocytes. J Physiol 455 623-640 Nazer MA, van Breemen C 1998 Functional linkage of Na+-Ca2+ exchange and sarcoplasmic reticulum Ca2+ release mediates Ca2+ cycling in vascular smooth muscle. Cell Calcium 24 275-283... 

ATP is used not only to power muscle contraction, but also to re-establish the resting state of the cell. At the end of the contraction cycle, calcium must be transported back into the sarcoplasmic reticulum, a process which is ATP driven by an active pump mechanism. Additionally, an active sodium-potassium ATPase pump is required to reset the membrane potential by extruding sodium from the sarcoplasm after each wave of depolarization. When cytoplasmic Ca2- falls, tropomyosin takes up its original position on the actin and prevents myosin binding and the muscle relaxes. Once back in the sarcoplasmic reticulum, calcium binds with a protein called calsequestrin, where it remains until the muscle is again stimulated by a neural impulse leading to calcium release into the cytosol and the cycle repeats. 

MH - Dantrolene may prevent changes within the muscle cell that result in MH syndrome by interfering with calcium release from the sarcoplasmic reticulum to the myoplasm. 

AMOUNT OF CALCIUM RELEASED FROM THE SARCOPLASMIC RETICULUM... 

Dantrolene interferes with the release of activator calcium through this sarcoplasmic reticulum calcium channel by binding to the RyRl and blocking the opening of the channel. Motor units that contract rapidly are more sensitive to the drug s effects than are slower-responding units. Cardiac muscle and smooth muscle are minimally depressed because the release of calcium from their sarcoplasmic reticulum involves a different RyR channel (RyR2). 

The carrier-mediated active transport system of calcium is responsible for the relaxation of muscle. However, the rate of efflux from sarcoplasmic reticulum membranes during reversal of the transport process is 102 to 104 orders too low to account for the massive calcium release from sarcoplasmic reticulum in stimulated muscle. Instead, passive diffusion of calcium across the sarcoplasmic reticulum membrane will proceed during excitation of muscle178,179,186. The rate of calcium release observed during excitation is 1.000-3.000 p moles/mg protein/min which is an increase of about 104 to 10s over the resting state. 

Hove-Madsen, L., Llach, A., Bayes-Genis, A., Roura, S., Rodriguez Font, E., Aris, A., and Cinca, J. (2004). Atrial Fibrillation is Associated with Increased Spontaneous Calcium Release from the Sarcoplasmic Reticulum in Human Atrial Myocytes. Circulation 110(11) 1358-63. 

Wehner, M., Rueffert, H., Koenig, F., and Olthoff, D. (2003a). Calcium Release from A Sarcoplasmic Reticulum is Facilitated in Human Myotubes Derived from Carriers of the Ryanodine Receptor Type 1 Mutations Ile2182Phe and Gly2375Ala. Genet Test 7(3) 203-11. 

Several of the eudistomins have been proved to induce calcium release from the sarcoplasmic reticulum (SR). The application of specific drugs which affect the Ca2+-releasing action from the SR is an effective approach to the resolution of an important problem in muscle biology concerning the... 

Abramson, J.J., Salama G. (1989). Critical sulfhydryls regulate calcium release from sarcoplasmic reticulum. J. Bioenerg. Biomembr. 21 283-94. 

Malignant hyperthermia is a frequently fatal condition that involves severe muscle contraction and hyperthermia. Episodes are triggered by stress and/or specific volatile anesthetics, such as halothane, which cause excessive calcium release from the sarcoplasmic reticulum. The disorder is caused by a mutation in the skeletal muscle ryanodine receptor. The physiological mechanism by which stress triggers malignant hyperthermia is not fully understood. 

Dantrolene is a hydantoin class of anticonvulsant that acts outside the central nervous system to produce skeletal muscle relaxation by interfering with excitation contraction coupling. In normally contracting muscle, activation of the ryanodine receptor within the muscle fiber results in calcium release from the sarcoplasmic reticulum and subsequent muscle contraction. Dantrolene interferes with the release of calcium from the sarcoplasmic reticulum by interfering with the ryanodine receptor. The release of calcium in smooth and cardiac muscle is under different control consequently, dantrolene primarily affects skeletal muscle. 

Ghosh et al. [48] have isolated two isoforms of nSMase from rabbit skeletal muscle (92 and 53 kDa). Peptide mapping revealed important structural similarities, and the catalytic activities were also similar, except that the 53 kDa protein was Mg" -independent. These nSMases are located in the transverse tubules of the muscle cells, which may be related to the observation that sphingosine modulates calcium release from sarcoplasmic reticulum membranes [49]. Two Mn -and Mg" -dependent nSMases located in the microsomal membranes of seminiferous tubes of immature Wistar rats have been characterized [50] whose properties do not appear to differ significantly from other mammalian nSMases. Finally, we mention two other nSMases purified from eukaryotic natural sources, namely the Mg -dcpcridcril nSMase isolated from Saccharomyces cerevisiae [51], and that obtained from membrane fractions of intraeryfhrocytic Plasmodium falciparum, the malaria parasite [52]. The latter enzyme was activated by phosphatidylserine and other anionic phosphohpids, and was sensitive to scyphostatin, an inhibitor of mammalian nSMase (see below). 

Nitric oxide, and perhaps 5-nitrosothiol, activates soinble gnanylate cyclase to increase intracellular concentrations of cyclic GMR Increased cychc GMP induces a sequence of protein phosphorylation associated with rednced intracellular calcium release from the sarcoplasmic reticulum or reduced permeability to extracellular calcium and, conseqnently, smooth muscle relaxation. 

Studies on skeletal muscle also support an intracellular site of action of the MDIs. Thus, pr-MDI (10 4m) significantly blocked caffeine-induced contractures of the rat diaphragm both in presence and in absence of extracellular calcium (33). Such caffeine-induced contractures are believed to be mediated by intracellular calcium mobilized from the sarcoplasmic reticulum or other intracellular calcium pool (34). Furthermore, bu-MDI (10 M) depresses activation heat in the frog sartorius muscle upon stimulation (35), indicating a reduction in the quantity of calcium released from the sarcoplasmic reticulum, since activation heat represents the energy liberated in association with calcium mobilization and sequestration in contracting muscle (36,... 

Dantrolene sodium is a skeletal muscle relaxant that affects contraction of muscle at a site beyond the myoneural junction and directly on the muscle itself it is believed to interfere with calcium release from sarcoplasmic reticulum ... 

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