Calcium cytosolic pool

Troponin is the regulatory complex of three proteins of the thin filament of myocytes. Troponin T binds to tropomyosin, troponin I is an inhibitory protein, and troponin C binds to calcium needed for muscle contraction. Following irreversible myocyte damage, unbound troponin subunits are initially released into blood from the cytosolic pools. This is followed by a sustained release of the tri-troponin complex due to the breakdown of the myocyte itself. Once in blood, the complex is further degraded into the binary troponin I-C complex, and frees troponin T. Figure 92.1 shows the kinetics of troponin subunit release. Troponin is superior to the other biomarkers for cardiac injury for two... 

Kiang JG, Smallridge RC. 1994. Sodium cyanide increases cytosolic free calcium evidence for activation of the reversed mode of the Na+/Ca2+ exchanger and Ca2+ mobilization from inositol trisphosphate-insensitive pools. Toxicol Appl Pharmacol 127(2) 173-181. 

Fig. 3. The interrelated changes in the metabolism of phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ during activation of the cell by a typical Ca2+-dependent hormone. R, receptor G, guanine regulatory protein PLC, phospholipase C DG, diacylglycerol CK, protein kinase C [Ca2+]sm, the Ca2+ concentration in a cellular domain just beneath the plasma membrane (striped area) Insl,4,SP3, inositol 1,4,5-trisphosphate Insl,3,4,5P4, inositol 1,3,4,5-tetrakisphosphate [Ca2+]c, cytosolic Ca2+ concentration CaM, calmodulin arrows (=>), fluxes of Ca2+ across membranes s=>, energy-dependent fluxes CaY, a calcium pool in specialized compartment of the endoplasmic reticulum. See text for discussion.

Although slightly attenuated, the rise in cytosolic calcium proceeds in the absence of extracellular calcium (as mentioned above), indicating that upon All stimulation calcium is released into the cytosol from an internal pool. The identity of this mobilized internal pool was initially inferred from cellular studies in which treatment with dantrolene inhibited the redistribution of intracellular calcium [39,40], Be-... 

The mobilization of calcium results not only in the observed transient rise in intracellular free calcium and enhanced cellular efflux, but also in a net loss of calcium from the cell (Fig. 1). Thus, total cell calcium declines with All stimulation of adrenal and vascular smooth muscle cells [44]. Furthermore, total cell calcium remains low throughout the duration of exposure to All, suggesting that the continued formation of small amounts of 1,4,5-IP3 prevents refilling of the ER pool. Upon the removal of All and the immediate reduction in IP3 concentration, total cell calcium rapidly recovers to prestimulation levels without a detectable change in cytosolic free calcium, as measured by calcium-sensitive dyes. This observation has been taken as evidence that the IP3-releasable ER pool is in direct communication with the plasma membrane and that extracellular calcium refills the pool without entering the bulk cytosol (see Ref. 45). The location of this pool within the cell (cytosolic vs. adjacent to the plasma membrane) remains a matter of controversy (see Rasmussen arid Barrett, Chapter 4). 

The concentration of free calcium ions (Ca " ) in the cytosol of ASM is central to the contractile response. The concentration of Ca in the cytosol is determined by the relative activity of processes which deliver Ca to the cytosol and which remove Ca " from it. Calcium may be delivered either by influx of extracellular Ca, or by release of Ca " stored in intracellular organelles, both processes involving the movement of Ca " down an electrochemical gradient from pools of high concentration. Conversely, Ca " is removed from the cytosol by energy-requiring pumps and by ion-exchange mechanisms which extrude extracellularly, or which refill the intracellular stores. 

Li Rinzel, 1994). The latter reductions therefore yield a minimal model for Ca oscillations, like the earlier, two-pool minimal model considered below, which takes into account only CICR and not the inhibition of Ca " release at high levels of cytosolic Ca. A one-pool version of this model in which Ca and IP3 behave as co-agonists for Ca " release is presented in section 9.4. A model based on the bellshaped calcium dependence of the ryanodine-sensitive calcium channel was recently proposed for calcium dynamics in cardiac myocytes (Tang Othmer, 1994b). 

It is well documented that N-formyl peptides induce a rapid, transient rise in intracellular calcium in neutrophils. It is also well established that inositol 1,4,5-trisphosphate released by the action of PLC triggers the release of Ca from intracellular stores. With the exception of the specific condition of neutrophils migrating on fibronectin and vitronectin [91], migration appears to occur in the absence of the intracellular calcium transient [196, 299, 456]. However, the studies that demonstrated this conclusion utilized indicators and buffers of cytosolic calcium that may not probe the entire calcium pool. Evidence suggests two additional mechanisms for regulating calcium that may have an impact on cell migration. 

Azaspiracid-1 increases cytosolic calcium and cAMP levels dependent on both the release of calcium from intracellular Ca pools and the influx from extracellular media through Ni -blockable channels. 

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