Ca2+-transporting systems

Figure 4 Schematic representation of the Ca2+-transporting systems affecting cellular calcium homeostasis during hormonal stimulation, oq = oq-adrenergic receptor VP = vasopressin receptor PLC = phospholipase C PI = phosphatidylinositol PIP = phospha-tidylinositol-4-phosphate PIP2 = phosphatidylinositol-4,5-biphosphate IP3 = inositol-1,4,5-triphosphate DG = diacylglycerol PKC = protein kinase C. (Modified from Refs. 125 and 285.)...

Opening of Ca2+ leads to a local increase in the cytosolic Ca2+ concentration from 10 7 M to 10 6 M. In this concentration region, the Ca2+ transport systems mentioned above work very efficiently. However, if an increase in Ca2+ concentration over 10 5 M takes place, e. g., because of cell damage, a level critical for the cell is reached. In this case, Ca2+ is pumped into the mitochondria with the help of Ca2+ transport systems localized in the inner membrane of the mitochondrion. 

Frolkis W, Frolkis RA, Mkhitarian LS et al. (1988) Contractile function and Ca2 + transport system of myocardium in aging. Gerontology 34(1-2) 64-74. 

Depending upon the mechanism that is employed by the organism to accumulate the solute, internalisation fluxes can vary both in direction and order of magnitude. The kinetics of passive transport will be examined in Section 6.1.1. Trace element internalisation via ion channels or carrier-mediated transport, subsequent to the specific binding of a solute to a transport site, will be addressed in Section 6.1.2. Finally, since several substances (e.g. Na+, Ca2+, Zn2+, some sugars and amino acids) can be concentrated in the cell against their electrochemical gradient (active transport systems), the kinetic implications of an active transport mechanism will be examined in Section 6.1.3. Further explanations of the mechanisms themselves can be obtained in Chapters 6 and 7 of this volume [24,245]. 

Figure 11.7 The microdomain concept of mitochondrial Ca2+ transport. Ca2+ penetrating from outside the cell or released from the ER generates local hotspots of high Ca2+ concentration in the vicinity of mitochondria sufficient to activate their low-affinity Ca2+ uptake system. (From Carafoli, 2002. Copyright (2002) National Academy of Sciences, USA.)...

Janik F, Wolf HU. 1992. The Ca2+-transport-ATPase of human erythrocytes as an in vitro toxicity test system—acute effects of some chlorinated compounds. J Appl Toxicol 12 351-358. 

Figure 6.13 The mechanisms for the elimination of Ca2+ from the cytoplasm sequestration into the ER via the Ca2+-ATPase system sequestration into the mitochondria (Mito) via the Ca2+ uni porter transport outside the cell via the Ca2+-ATPase system ion gradient-driven transport outside the cell via the Ca2+/NaH exchanger. Abbreviations ER, endoplasmic reticulum.

The fact that Mn2+ may also be used105 as a probe for Ca2+ serves to emphasize those problems, as Ca2+ and Mg2+ tend to be mutually inhibitory. It appears that Mn2+ resembles Ca2+ in terms of movement in and out of certain cells. However, Mn2+ is taken up by some microbes through low affinity magnesium transport systems. These organisms usually have specific high affinity transport systems for Mn2+ as well.106... 

The best studied example of a Group IIA cation transport system is the calcium pump of the sarcoplasmic reticulum of skeletal muscle. Indeed, the calcium pump and the sodium pump represent the most studied of all transport processes. The calcium pump involves a membrane-bound (Ca2+, Mg2+)-ATPase and uptake of Ca2+ is associated with hydrolysis of ATP. While the... 

Biological and Medical Aspects 62.1.3,3.2 Miscellaneous mammalian transport systems for Ca2+... 

A variety of other calcium transport systems are associated with Ca21-activated ATPases. The extraembryonic structure, the chorioallantoic membrane, of the chick embryo is responsible for the translocation of over 120 mg of eggshell calcium into (he embryo during development. The enzyme responsible for this is a (Ca2+, Mg2+)-ATPase with Km values for Ca2+ of 30 p,mol dm-3 and 0.3 mmol dm-3, and a molecular weight of 170 000. The enzyme can be crossiinked and co-isolated with a calcium-binding protein.158 Transport of Ca2+ is also associated with (Ca2+, Mg2+)-ATPases in neutrophil plasma membranes,159 transverse tubule membranes from rabbit skeletal muscle,160 rabbit myocardial membrane,161 endoplasmic reticulum,162 sar-colemma,163 brain microsomes,164 the Golgi apparatus165 and rat liver plasma membranes.166... 

Recently, a second transport system for efflux of Ca2+ from E. coli has been identified.190 This is a calcium-phosphate symporter, which catalyzes a 1 1 cotransport of calcium and phosphate, probably in exchange for protons. 

All molecular systems involved in Ca2+ homeostatic processes are regulated by Ca2+ itself, which operates numerous feedback loops. That is, increase in cytosolic Ca2+ concentration induces a Ca2+-dependent inactivation of voltage-operated plasmalemmal Ca2+ channels. Fluctuations in [Ca2+]L differentially regulate Ca2+ transport across the endomembrane elevation of [Ca2+]L increases the susceptibility of RyRs and InsP3Rs to activation, and inhibits the SERCAs when [Ca2+]L falls, the SERCA pumping is much activated, and the Ca2+ release channels are inhibited (Burdakov et al., 2005 Burdakov and Verkhratsky 2006). 

The NaCl transport system in the luminal membrane of the thick ascending limb is a Na+/K+/2CF cotransporter (Figure 15-4). This transporter is selectively blocked by diuretic agents known as "loop" diuretics (see below). Although the Na+/K+/2CF transporter is itself electrically neutral (two cations and two anions are cotransported), the action of the transporter contributes to excess K+ accumulation within the cell. This results in back diffusion of K+ into the tubular lumen and development of a lumen-positive electrical potential. This electrical potential provides the driving force for reabsorption of cations—including Mg2+ and Ca2+—via the paracellular pathway (between the cells). Thus, inhibition of salt transport in the thick ascending limb by loop diuretics causes an increase in urinary excretion of divalent cations in addition to NaCl. 

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