Ryanodine receptors calcium release from intracellular

The current study shows that phthalic acid diamide insecticides, represented by flubendiamide and its sulfoxide analogue, activated ryanodine receptors present in isolated Heliothis neurons, as concluded from the following results. Firstly, calcium transients evoked by phthalic acid diamides were independent of the extracellular [Ca ], in contrast to the signals elicited by acetylcholine. This was interpreted as calcium release from intracellular stores of the endo(sarco)plasmic reticulum, which could in principle be mediated by two different release channels, namely the ryanodine receptor and the IP3 receptor. 

Figure 2. A proposed model demonstrating several different prominent calcium-related pathways whose activity may be altered in dystrophic muscle. Increased activity of mechanosensitive channels (MS) and store-activated channels (SOC), which are likely derived from the same gene product (TRPC), and the calcium leak channel, which could represent a proteolyzed TRPC SOC channel. Decreased mechanical coupling between L-type VGCC and ryanodine receptors may increase basal calcium release from calcium stores (not shown). Further, increased IP, and IP, receptor levels may also enhance basal and stimulated calcium-induced calcium release (CICR) from calcium stores. Calcium store depletion can increase translocation of SOCs from intracellular vesicles to the sarcolemma. Finally, the relationship between increased membrane fragility and tearing is less certain, but calcium influx through sarcolemmal tears could lead to calcium-dependent proteolysis and increased activity of calcium leak channels, as well as proteolysis of other targets, and increased release of calcium from intracellular stores through CICR. This model is not meant to be comprehensive, and other calcium-related molecules are discussed in the text...

Ullmer C, Boddeke HG, Schmuck K, Lubbert H. 5-HT2B receptor-mediated calcium release from ryanodine-sensitive intracellular stores in human pulmonary artery endothelial cells. Br J Pharmacol 1996 117 1081-1088. 

Figure 1. Model of signal transduction in the snake VN system. Ligand binding to a G-protein (G)-coupled receptor (R) activates a phosphatidyl inositol-specific phospholipase C (PLC) which, in turn, hydrolyzes phosphatidyl inositol 4,5-bisphosphate (PIP2) producing diacylglyserol (DAG) and 1,4,5-inositol trisphosphate (IP3). IP3 acts directly on IP3 receptors on the smooth endoplasmic reticulum to release calcium (Ca ) from intracellular stores and on an IP3- sensitive Ca channel in the cell membrane allowing calcium influx from the extracellular space. The elevated levels of intracellular Ca results in activation of the ryanodine receptor (RyR) on the membrane of the endoplasmic reticulum, resulting in additional Ca release from intracellular stores, a phenomenon known as calcium-induced calcium release (CICR). Intracellular Ca levels return to prestimulation levels by efflux of Ca and influx of sodium (NA ) through a NAV Ca exchanger.

Ducreux, S., Zorzato, F., Muller, C., Sewry, C., Muntoni, F., Quinlivan, R., Restagno, G., Girard, T., and Treves, S. (2004). Effect of Ryanodine Receptor Mutations on Interleukin-6 Release and Intracellular Calcium Homeostasis in Human Myotubes from Malignant Hyperthermia-Susceptible Individuals and Patients Affected by Central Core Disease. J Biol Chem 279(42) 43838 16. 

The skeletal muscle ryanodine receptor, RyRl, controls the release of calcium, through a central channel, from the intracellular sarcoplasmic reticulum [34], The channel forms at the convergence of four identical protein subunits each of which contains two a-helices. One helix from each subunit is approximately 0.45 nm long and has a central kink. The overall effect is to give the channel a funnel-like entrance about 0.3 nm across leading to a central pore with a 0.15 nm diameter. The pore is defined by four further a-helices approximately 0.22 nm long, one from each subunit. Unfortunately the low resolution of the structure does not allow for detailed study of the filtering mechanism. 

In striated muscle, the sheer amount of filaments is such that we actually need quite a bit of calcium to swiftly saturate the troponin molecules and trigger contraction. The lion s share of this calcium is not obtained from the extracellular space (viathe voltage-gated Ca channel, the dihydropyridine receptor - see later) but from the intracellular storage, more specifically from the endoplasmic reticulum, which somebody found necessary to christen sarcoplasmic reticulum in the muscle cell (gr. sarx, sarkos = flesh). It is released from there by a specialized Ca channel, the ryanodine receptor (RyR). This channel is activated by cytosolic calcium, which of course creates a fast and powerful... 

Caffeine is apparently influential on other ion transport process that are not under the control of adenosine receptors or affected by ryanodine. It increases the concentration of free calcium ion in pancreatic beta cells and also inhibits potassium channels [494]. Sparteine has a similar effect on the same cells [495]. In another example caffeine stimulates release of calcium from intracellular stores in liver cells and is not competitive with ryanodine [496]. Senecionine acts similarly [497]. Conversely, caffeine inhibits a calcium channel in rat cerebellar microsomes [212]. 

Figure 18. Current model of mechanisms postulated to participate in generation of calcium transients during stimulation of snake VN neurons with chemoattractants in ESS. Initially ESS activates receptors that trigger IP3 production, mediating an increase in cytosolic Ca through simultaneous release of Ca from intracellular stores and influx through a PLC-dependent channel in the plasma membrane. There is additional Ca release from ryanodine-sensitive stores through a calcium-induced calcium release mechanism. Normal cytosolic levels of Ca are restored by activation of the Na+/ Ca exchanger.

Ryanodine receptors (RyR) mediate the release of calcium from intracellular stores of the sarcoplasmic/endoplasmic reticulum (SR/ER) following a small calcium influx via voltage-gated calcium channels of the cytoplasmic membrane after depolarization. The process, referred to as calcium-induced calcium release, triggers muscle contraction after electrical excitation in mammalian cardiac as well as in insect striated muscles (I). Three RyR isoforms exist in mammals Type 1, which is predominantly expressed in skeletal muscles Type 2, which is expressed in cardiac muscle and the more ubiquitously expressed Type 3 2 . 

Ryanodine receptors are a family of intracellular Ca release channels that were originally identified in the sarcoplasmic reticulum of skeletal muscle cells. Three members of the family were distinguished, RyR2 ryanodine receptors in the cardiac muscle. RyRl (in the skeletal muscle) and RyR2 function as Ca release chaimels from the sarcoplasmic reticulum intracellular calcium store and play a crucial role in the exdtation-contraction cycle. They bind and calmodulin and become phosphorylated by various protein kinases including Ca /calmodulin- and cAMP-dependent kinases (Lokuta etal. 1995, Mayrleitner etal. 1995). 

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