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Ca2+ Transporters (ca2+ + transporter)
Selected AbstractsPartitioning of the plasma membrane Ca2+ -ATPase into lipid rafts in primary neurons: effects of cholesterol depletionJOURNAL OF NEUROCHEMISTRY, Issue 2 2007Lei Jiang Abstract Spatial and temporal alterations in intracellular calcium [Ca2+]i play a pivotal role in a wide array of neuronal functions. Disruption in Ca2+ homeostasis has been implicated in the decline in neuronal function in brain aging and in neurodegenerative disorders. The plasma membrane Ca2+ -ATPase (PMCA) is a high affinity Ca2+ transporter that plays a crucial role in the termination of [Ca2+]i signals and in the maintenance of low [Ca2+]i essential for signaling. Recent evidence indicates that PMCA is uniquely sensitive to its lipid environment and is stimulated by lipids with ordered acyl chains. Here we show that both PMCA and its activator calmodulin (CaM) are partitioned into liquid-ordered, cholesterol-rich plasma membrane microdomains or ,lipid rafts' in primary cultured neurons. Association of PMCA with rafts was demonstrated in preparations isolated by sucrose density gradient centrifugation and in intact neurons by confocal microscopy. Total raft-associated PMCA activity was much higher than the PMCA activity excluded from these microdomains. Depletion of cellular cholesterol dramatically inhibited the activity of the raft-associated PMCA with no effect on the activity of the non-raft pool. We propose that association of PMCA with rafts represents a novel mechanism for its regulation and, consequently, of Ca2+ signaling in the central nervous system. [source] Plasma membrane Ca2+ -ATPase in the cilia of olfactory receptor neurons: possible role in Ca2+ clearanceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2007Karen Castillo Abstract Olfactory sensory neurons respond to odorants increasing Ca2+ concentrations in their chemosensory cilia. Calcium enters the cilia through cAMP-gated channels, activating Ca2+ -dependent chloride or potassium channels. Calcium also has a fundamental role in odour adaptation, regulating cAMP turnover rate and the affinity of the cyclic nucleotide-gated channels for cAMP. It has been shown that a Na+/Ca2+ exchanger (NCX) extrudes Ca2+ from the cilia. Here we confirm previous evidence that olfactory cilia also express plasma membrane Ca2+ -ATPase (PMCA), and show the first evidence supporting a role in Ca2+ removal. Both transporters were detected by immunoblot of purified olfactory cilia membranes. The pump was also revealed by immunocytochemistry and immunohistochemistry. Inside-out cilia membrane vesicles transported Ca2+ in an ATP-dependent fashion. PMCA activity was potentiated by luminal Ca2+ (K0.5 = 670 nm) and enhanced by calmodulin (CaM; K0.5 = 31 nm). Both carboxyeosin (CE) and calmidazolium reduced Ca2+ transport, as expected for a CaM-modulated PMCA. The relaxation time constant (,) of the Ca2+ -dependent Cl, current (272 ± 78 ms), indicative of luminal Ca2+ decline, was increased by CE (2181 ± 437 ms), by omitting ATP (666 ± 49 ms) and by raising pH (725 ± 65 ms), suggesting a role of the pump on Ca2+ clearance. Replacement of external Na+ by Li+ had a similar effect (, = 442 ± 8 ms), confirming the NCX involvement in Ca2+ extrusion. The evidence suggests that both Ca2+ transporters contribute to re-establish resting Ca2+ levels in the cilia following olfactory responses. [source] Murine TNF,ARE Crohn's disease model displays diminished expression of intestinal Ca2+ transportersINFLAMMATORY BOWEL DISEASES, Issue 6 2008Sylvie Huybers MSc Abstract Background: Patients suffering from Crohn's disease (CD) show increased incidence of low bone mineral density. Investigating this complication is difficult because the exact etiology of CD remains elusive. Mice carrying a deletion in the tumor necrosis factor (TNF) AU-rich elements (ARE) are reported as a model for human CD and are characterized by elevated TNF-, levels and inflammations in the terminal ileum. To evaluate whether these mice have a Ca2+ handling problem, this study analyzed the Ca2+ homeostasis in heterozygous TNF,ARE mice (TNF,ARE/+) in comparison to wildtype littermates. Methods: Beside serum Ca2+ and vitamin D levels, the expression of Ca2+ transporters was analyzed in intestine, kidney and bone using quantitative real-time PCR, Western blot and immunohistochemistry. Bone scans were performed to measure bone parameters. Results: Ca2+ transporters in duodenum (TRPV6, calbindin-D9K, PMCA1b) and kidney (TRPV5, calbindin-D28K, NCX1) showed significantly reduced mRNA expression levels in TNP,ARE/+ mice, except for renal TRPV5. In bone, only calbindin-D9K mRNA displayed a significant down-regulation. These findings were supported by declined duodenal calbindin-D9K and renal calbindin-D28K protein values. Likely, this down-regulation of Ca2+ transporters in TNP,ARE/+ mice is mediated by the 58 ± 9% reduction in serum 1,25(OH)2D3 levels. Diminished expression of Ca2+ transporters combined with unchanged serum Ca2+ levels assumes Ca2+ loss from bone to compensate for the body's overall Ca2+ shortage. Indeed, microcomputed tomography scanning demonstrated reduced trabecular and corticol bone thickness and volume in TNF,ARE/+ mice. This finding is further supported by increased total deoxypyridinoline in serum. Conclusions: Our results imply that TNF,ARE/+ mice have a disturbed Ca2+ homeostasis characterized by reduced duodenal and renal Ca2+ transporters, diminished 1,25(OH)2D3 levels, and increased bone resorption associated with profound bone abnormalities. (Inflamm Bowel Dis 2008) [source] | ||||||||||