Smooth endoplasmic reticulum calcium

The smooth endoplasmic reticulum calcium pumps (SERCA) found in brain were first identified in sarcoplasmic reticulum. The three isoforms of SERCA are products of separate genes SERCA-1 is expressed in fast-twitch skeletal muscle SERCA-2a in cardiac/slow-twitch muscle SERCA-2b, an alternatively spliced form, is expressed in smooth muscle and non-muscle tissues SERCA-3 is... 

Calcium ions (Ca ) are important for the mediation of hepatic injury. Cytosolic free calcium is maintained at relatively low concentrations compared to the extracellular levels. The majority of intracellular calcium is sequestered within the mitochondria and endoplasmic reticulum. Membrane associated calcium and magnesium ATPases are responsible for maintaining the calcium gradient (Farrell et ah, 1990). Significant and persistent increases in the intracellular calcium result from nonspecific increases in permeability of the plasma membrane, mitochondrial membranes, and membranes of the smooth endoplasmic reticulum. Calcium pumps in the mitochondrial membrane require NADPH, thus depletion of available NADPH can cause calcium release from mitochondria (Cullen, 2005). 

Figure 2. Reporting of cytosolic free calcium levels by indo-1. Increases in cytosolic calcium, due either to entry of extracellular calcium via calcium channels or to release of intracellular calcium sequestered in organelles such as smooth endoplasmic reticulum, results in formation of the indo-l-calcium complex. Fluorescence intensity at 400 nm (excitation at 340 nm) is proportional to the concentration of this complex the dissociation constant for this complex is about 250 nff (24), making this probe useful for detecting calcium activities in the range of 25 to 2500 nJ. ...

Figure 3. Reporting of intracellular calcium sequestration by chlorotetracycline (CTC). CTC preferentially partitions into cell membranes and its fluorescence in this environment is sensitive to calcium bound to the membrane therefore its signal (excitation AOO nm, emission 530 nm) will come largely from organelles that bind or sequester calcium, such as smooth endoplasmic reticulum or mitochondria. Release of calcium from such organelles is accompanied by dissociation of the calcium-CTC complex, a decrease in CTC fluorescence and efflux of unbound probe from the organelle and from the cell.

The endoplasmic reticulum (ER) is responsible for the production of the protein and lipid components of most of the cell s organelles. The ER contains a large number of folds, but the membrane forms a single sheet enclosing a single closed sac. This internal space is called the ER lumen. The smooth endoplasmic reticulum (ER) in muscle cells contains the vesicles and tubules that serve as a store of calcium ions. These are released as one step in the muscle contraction process. Calcium pumps, Ca +-ATPases, serve to move the calcium from the cytoplasm to the ER or SR lumen. 

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.

In the sarcoplasm of smooth muscle cells there is a membrane bound compartment usually referred to as the SR by analogy with skeletal muscle. However, it is not at all clear that the interior of these membrane-bound regions are continuous as they are in skeletal muscle. The primary properties of this system seem to be quite similar to those of the endoplasmic reticulum of many other cell types. In general, calcium is concentrated into the membrane-bound reticulum and then released to initiate the characteristic action of the cell. 

Raeymaekers L, Verbist J, Wuytack F, Plessers L, Casteels R 1993 Expression of Ca2+ binding proteins of the sarcoplasmic reticulum of striated muscle in the endoplasmic reticulum of pig smooth muscles. Cell Calcium 14 581-589... 

Schmidt, T., Zaib, F., Samson, S.E., Kwan, C.Y., and Grover, A.K. 2004. Peroxynitrite resistance of sarco/endoplasmic reticulum Ca2+ pump in pig coronary artery endothelium and smooth muscle. Cell Calcium 36 77-82. 

The answer is c. (Murray, pp 238-249. Scriver, pp 2367-2424. Sack, pp 159-175. Wilson, pp 287-317.) A variety of agonists activate the plasma membrane-bound enzyme phospholipase C, which hydrolyzes the phosphodiester bond of phosphatidyl inositol 4,5-bisphosphate and consequently releases diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). Phospholipase C is also known as phosphoinositidase and as polyphosphoinositide phosphodiesterase. Both DAG and IP3 are second messengers. DAG activates protein kinase C, which is important in controlling cell division and cell proliferation. IP3 opens calcium channels and allows the rapid release of the calcium stores in endoplasmic reticulum (in smooth muscle, sarcoplasmic reticulum). The elevated levels of calcium ion stimulate smooth-muscle contraction, exocytosis, and glycogen breakdown. 

Three mammalian PLC subtypes O four isoforms, -y two isoforms, 8 four isoforms) have been isolated, but only the PLC-P family appears to be regulated directly by G-proteins. IP3 binds to endoplasmic membrane receptors and liberates the calcium from the sequestered stores (endoplasmic reticulum) inducing an increase of cytoplasmic calcium. An elevation of free calcium in the cell can induce, for example, a smooth muscle contraction, secretion from exocrine glands and transmitter release. 

Attempts to compensate for impaired calcium signaling due to reduced endoplasmic reticulum Ca ATPase fimction, include enhanced calcium entry through L-type calcium channels and store-operated channels in vascular smooth muscle cells in SHR (Tabet et al., 2004 Fellner and Arendshorst, 2002). Impaired vascular... 

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