Calcium stores

NADP can be converted to nicotinic acid adenine dinucleotide phosphate (NAADP), which has distinct functions in the regulation of intracellular calcium stores. The studies of these new roles of NAD(P) in metabolism are in their early stages, but they might soon help to better understand and explain the symptoms of niacin deficiency ( pellagra) [1]. 

However, the total regulatory system is not so simple and linear. In skinned muscle preparations especially, it can be shown that there are calcium stores which cannot be released by IP3 but which are released by elevated levels of calcium itself That is, by the mechanism of calcium induced calcium release (CICR). The CICR... 

The ion channel receptors are relatively simple in functional terms because the primary response to receptor activation is generated by the ion channel which is an integral part of the protein. Therefore, no accessory proteins are needed to observe the response to nicotinic AChR activation and the full functioning of the receptor can be observed by isolating and purifying the protein biochemically and reconstituting the protein in an artificial lipid membrane. In contrast, the G-protein-coupled receptors require both G-proteins and those elements such as phospholipase-C illustrated in Fig. 3.1, in order to observe the response to receptor activation (in this case a rise in intracellular calcium concentration resulting from the action of IP3 on intracellular calcium stores). 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

If some of the electrophysiological effects of oxidant stress occur secondary to an elevation in intracellular calcium, it is important to consider the possible factors that may underlie the initial elevation of calcium. In the simplest analysis, elevation of cytosolic calcium may be due to (1) redistribution of intracellular calcium stores (2) increased calcium influx or (3) decreased calcium efflux. 

Calcium oxalate (723) occurs as the monohydrate (whewellite, the thermodynamically stable form under ambient conditions (724)), the dihydrate (weddellite) in plant calcium stores and in sap, or the trihydrate (725). Calcium oxalate also plays a structural role in plants. Oxalate, for example from excessive amounts of rhubarb or spinach, inhibits absorption of Ca2+ from the GIT precipitation of calcium oxalate is the reason for the toxicity of oxalates. Calcium oxalate may also occur in man, where it can appear as minute star-shaped crystals in the urine. It is the main constituent of the majority of urinary calculi in man (726,727). The relationships between dietary calcium... 

Two general mechanisms have been considered by which a depleted intracellular Ca2+ pool might communicate with the plasma membrane [4]. There is evidence that the IP3 receptor is associated with the cytoskeleton, and this association may tether the IP3 receptor to the plasma membrane. Depletion of intracellular calcium stores might cause a conformational change in the IP3 receptor, which could be conveyed to the plasma membrane via the cytoskeleton or by a more direct protein-protein interaction. Alternatively, signaling could occur... 

However, there are some inconsistencies with the idea that the IP3-sensitive calcium store and the ER are entirely coincident. For one, there is really no correlation between... 

Pozzan, T., Rizzuto, R., Volpe, P. and Meldolesi, J. Molecular and cellular physiology of intracellular calcium stores. Physiol. Rev. 74 595-636,1994. 

Rossier, M. F. and Putney, J. W. Jr. The identity of the calcium storing inositol 1,4,5-trisphosphate-sensitive organelle in non-muscle cells Calciosome, endoplasmic reticulum... or both Trends Neurosci. 14 30-314,1991. 

Broderick R, Broderick KA 1990 Ultrastructure and calcium stores in the myometrium. In Carsten ME, Miller JD (eds) Uterine function molecular and cellular aspects. Plenum Press, New York, p 1-70... 

Martin C, Hyvelin JM, Chapman KE, Marthan R, Ashley RH, Savineau JP 1999 Pregnant rat myometrial cells show heterogeneous ryanodine- and caffeine-sensitive calcium stores. Am J Physiol 277 C243-C252... 

Wayman CP, McFadzean I, Gibson A, Tucker JF 1996 Two distinct membrane currents activated by cyclopiazonic acid-induced calcium store depletion in single smooth muscle cells of the mouse anococcygeus. Br J Pharmacol 117 566—572... 

Wayman CP, Gibson A, McFadzean I 1998 Depletion of either ryanodine- or IP3-sensitive calcium stores activates capacitative calcium entry in mouse anococcygeus smooth muscle cells. Pfliiger s Arch 435 231—239... 

James PF, Grupp IL, Grupp G et al 1999 Identification of a specific role for the Na,K-ATPase a2 isoform as a regulator of calcium in the heart. Mol Cell 3 555—563 Janiak R, Wilson, SM, Montague S, Hume JR 2001 Heterogeneity of calcium stores and elementary release events in canine pulmonary arterial smooth muscle cells. Am J Physiol 280 C22-C33... 

Parekh AB, Penner R 1997 Store depletion and calcium influx. Physiol Rev 77 901-930 Potocnik SJ, Hill MA 2001 Pharmacological evidence for capacitative Ca2+ entry in cannulated and pressurized skeletal muscle arterioles. Br J Pharmacol 134 247-256 Pozzan T, Rizzuto R, Volpe P, Meldolesi J 1994 Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 74 595—636 Putney JW Jr, Broad LM, Braun FJ, Lievremont JP, Bird GS 2001 Mechanisms of capacitative calcium entry. J Cell Sci 114 2223—2229... 

In a study by Fincke and Sherman (JL3), the calcium of spinach was not utilized as well as that from milk however, the calcium of kale, which is low in oxalic acid (3,4), was about as available as that from milk. The calcium utilization factor was determined by dividing the weight of calcium stored by the weight of calcium ingestion. Rats 4 weeks old were fed for 60 days a diet in which most of the calcium was supplied by skim milk, or in which half of the skim milk was replaced by dried spinach or dried kale in amounts to provide the same amount of calcium. The diets contained about 0.3% calcium and 10% butter fat. It was concluded that the poor utilization of the calcium of spinach was due to the oxalic acid in spinach. 

Stuart RO, Sun A, Bush KT, and Nigam SK [1996] Dependence of epithelial intercellular junction biogenesis on thapsigargin-sensitive intracellular calcium stores. J Biol Chem 271 13636-13641... 

CoUin T, Matty A, Llano 1 (2005) Presynaptic calcium stores and synaptic transmission. Curr Opin Neurobiol 15 275-281... 

Emptage NJ, Reid CA, Fine A (2001) Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca + entry, and spontaneous transmitter release. Neuron 29 197-208... 

The sER also functions as an intracellular calcium store, which normally keeps the Ca level in the cytoplasm low. This function is particularly marked in the sarcoplasmic reticulum, a specialized form of the sER in muscle cells (see p. 334). For release and uptake of Ca " ", the membranes of the sER contain signal-controlled Ca channels and energy-dependent Ca ATPases (see p. 220). In the lumen of the sER, the high Ca " " concentration is buffered by Ca -binding proteins. 

As the human body is able to store many minerals, deviations from the daily ration are balanced out over a given period of time. Minerals stored in the body include water, which is distributed throughout the whole body calcium, stored in the form of apatite in the bones (see p. 340) iodine, stored as thyroglobulin in the thyroid and iron, stored in the form of ferritin and hemosiderin in the bone marrow, spleen, and liver (see p. 286). The storage site for many trace elements is the liver. In many cases, the metabolism of minerals is regulated by hormones—for example, the uptake and excretion of H2O, Na, ... 

PTH is secreted from the parathyroid glands in response to a low plasma concentration of ionized (free) calcium. PTH immediately causes the transfer of labile calcium stores from bone into the bloodstream. PTH increases rates of dietary calcium absorption by the intestine indirectly via the vitamin D3 system activation of enterocyte activity. Within the kidney, PTH directly stimulates calcium reabsorption and a phosphate diuresis. 

Calcium ion facilitates the toxic actions of cardiac glycosides by accelerating the overloading of intracellular calcium stores that appears to be responsible for digitalis-induced abnormal automaticity. Hypercalcemia therefore increases the risk of a digitalis-induced arrhythmia. The effects of magnesium ion appear to be opposite to those of calcium. These interactions mandate careful evaluation of serum electrolytes in patients with digitalis-induced arrhythmias. 

Diagram of the structures involved in the stretch reflex arc. I is an inhibitory interneuron E indicates an excitatory presynaptic terminal la is a primary intrafusal afferent fiber Ca2+ denotes activator calcium stored in the sarcoplasmic reticulum of skeletal muscle RyR channels indicates the Ca2+ release channels. 

Peracchia C Possible involvement of caffeine and ryanodine-sensitive calcium stores in low pH-induced regulation of gap junction channels in Peracchia C (ed) Biophysics of Gap Junction Channels. Boca Raton, CRC Press, 1991a, pp 13-28. 

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