Extracellular calcium concentration

Artursson P, C Magnusson. (1990). Epithelial transport of drugs in cell culture. II. Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells. J Pharm Sci 79 595-600. 

Modification of extracellular calcium concentration or of calcium entry therefore can markedly affect neurotransmission. 

Extracellular calcium is required to give maximum LH stimulated steroidogenesis in isolated Leydig cells [15,18]. Using the intracellular fluorescent calcium indicator, Quin 2, it has been shown that lowering the extracellular calcium concentration from 2.5 mM to 1.1 xM lowered the LH stimulated intracellular calcium concentrations from 300-500 nM to only 52 nM. These studies showed that LH increases intracellular calcium and that this increase is dependent mainly on extracellular levels of calcium. Cyclic AMP analogues were also shown to increase intracellular calcium to the same concentrations as those obtained with LH, indicating that cyclic AMP is one of the mediators of LH action on calcium mobilization [15]. 

In testis Leydig cells the LH stimulated cyclic AMP production was unaffected by lowering the extracellular calcium concentration [15]. However, three inhibitors of calmodulin all inhibited LH stimulated cyclic AMP production, indicating that there may well be a requirement for calcium. In swine granulosa cells, calcium deprivation suppressed the LH dose-dependent accumulation of cyclic AMP by 50% [29]. 

Calcium performs a variety of cellular functions in muscle and nerve that ultimately result in muscular contraction. Excellent descriptions of calcium s function in muscle and nerve are to be found in the reviews by Hoyle (37), Cohen (38), and Robertson (39). At the neuromuscular junction, the excitable cells are very sensitive to changes in extracellular concentrations of calcium. Curtis (40) and Luttgau (41) described a fall in the resting action potential and electrical resistance when the extracellular calcium concentration fell below 10 M. The action potential and electrical resistance returned to normal following addition of calcium to this vitro preparation. The magnitude of the Initial muscle membrane action potential, that which regulates the propagation of further muscle contraction, is also mediated by the extracellular calcium concentration. While the inward flow of sodium ions from the extracellular space remains the dominant factor in the mechanism of muscle membrane depolarization, calcium ion flux appears to mediate the cell s permeability to sodium ions. This effect is particularly true in cardiac tissue (W). 

The CaR is expressed in many cells such as parathyroid cells and C cells in the thyroid gland. It is also expressed in the kidneys, osteoblasts, in the gastrointestinal mucosa, and hematopoietic cells in bone marrow. It has been found that CaR is expressed in different amounts on the cell face of many cell types and in diverse species. CaR is a member of the G protein-coupled receptor family with seven hydrophobic transmembrane helices in the plasma membrane. It has a large N-terminal domain with about 600 amino acids located in the extracellular environment and is essential for sensing extracellular calcium concentration. CaR has a large cytosolic C-terminal domain with about 200 amino acids that is subjected to phosphorylation. A dimeric structure has been proposed based on the known crystal structure of the metabotropic glutamate receptor type 1. 

D. V. Fitzpatrick, M. Karmazyn, Comparative effects of calcium channel blocking agents and varying extracellular calcium concentration on hypoxia/reoxygenation and ischemia/reperfusion-induced cardiac injury, J Pharmacol Exp Ther 28, 761-768 (1984). 

Vitamin D and its metabolites play an important role in the maintenance of extracellular calcium concentrations and in normal skeletal structure and mineralization. Vitamin D is necessary for the optimal absorption of calcium and phosphorus. On a worldwide basis, the most common cause of hypocalcemia is nutritional vitamin D deficiency. In malnourished populations, manifestations include rickets and osteomalacia. Nutritional vitamin D deficiency is uncommon in Western societies because of the fortification of miUc with ergocalciferol. " The most common cause of vitamin D deficiency in Western societies is gastrointestinal disease. Gastric surgery, chronic pancreatitis, small-bowel disease, intestinal resection, and bypass surgery are associated with decreased concentrations of vitamin D and its metabolites. Vitamin D replacement therapy may need to be administered by the intravenous route if poor oral bioavailability is noted. Decreased production of 1,25-dihydroxyvitamin D3 may occur as a result of a hereditary defect resulting in vitamin D-dependent rickets. It also can occur secondary to chronic renal insufficiency if there is insufficient production of the 1 -a -hydroxylase enzyme for the... 

All nicotinic receptors are somewhat calcium permeable the most permeable are neuronal homomeric receptors (a7, a9) and the least permeable, embryonic muscle receptors. It must be noted that the measurement of relative calcium permeability by the simplest technique (reversal potential shift induced by changes in extracellular calcium concentrations) is error-prone for neuronal nicotinic receptors because their extreme inward rectification makes it difficult to measure reversal potentials accurately. A further technical difficulty (for recombinant receptors) arises from the presence in Xenopus oocytes of a calcium-dependent chloride conductance that has to be suppressed or minimized by either intracellular calcium chelation or chloride depletion. Some of these problems can be overcome by expressing the receptors in mammalian cell lines and using ratiometric measurements of intracellular calcium and coupled with wholecell recording, to obtain a measure of what proportion of the nicotinic current is carried by calcium (a measure that also has the advantage of being physiologically more relevant). 

Leweke FM, Louvel J, Rausche G, Heinemann U (1990) Effects of pentetrazol on neuronal activity and on extracellular calcium concentration in rat hippocampal slices. Epilepsy Res 6 187-198. 

At the same time serotonin increases the permeability to calcium. Since the extracellular calcium concentrations are much higher than that of the cytosol, the net result is a flow of calcium from the extracellular fluid into the cytosol. cAMP stimulates secretion... 

An additional mechanism exposed in the VDR KO mouse is the defect in Thl-related production of INFy, presumably because of defective IL-18 production by macrophages and reduced STAT4 expression in T cells, per se (O Kelly et al. 2002). Another important aspect of the immune defects in VDR" mice is that many of them can be corrected by normalization of extracellular calcium concentrations following a high calcium and lactose diet (Bouillon et al. 2008). Finally, myelopoiesis appears normal in the VDR KO mouse (O Kelly et al. 2002). 

Konopacki J, Maciver MB, Bland BH, Roth SH (1987) Carbachol-induced EEG theta activity in hippocampal brain shces. Brain Res 405 196-198 Kroker KS, Rosenbrock H, Rast G (2011) A multi-slice recording system for stable late phase hippocampal long-term potentiation experiments. J Neurosci Methods 194 394- 1 Leweke FM, Louvel J, Rausche G, Heinemann U (1990) Effects of pentetrazol on neuronal activity and on extracellular calcium concentration in rat hippocampal slices. Epilepsy Res 6 187-198... 

PTH is a single-chain polypeptide that is released from the parathyroid when there is a decrease in the calcium concentration in extracellular fluid. The calcium-sensing receptor (acting as the thermostat for calcium) is found on the parathyroid gland, where it detects small perturbations in serum ionized calcium. The decline in serum calcium induces an increase in PTH secretion. PTH has the effect of restoring extracellular calcium concentrations by stimulating the resorption of bone to release... 

Dvorak, M. M., Siddiqua, A., Ward, D. T., Carter, D. H., Dallas, S. L., Nemeth, E. E, and Riccardi, D. 2004. Physiological changes in extracellular calcium concentration directly control osteoblast function in the absence of calciotropic hormones. Proc Natl Acad Sci USA, 101,5140-5145. 

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