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Ca2+ Entry Pathways (ca2+ + entry_pathway)
Selected AbstractsCalcium Channel TRPV6 Is Involved in Murine Maternal,Fetal Calcium Transport,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2008Yoshiro Suzuki Abstract Maternal,fetal calcium (Ca2+) transport is crucial for fetal Ca2+ homeostasis and bone mineralization. In this study, the physiological significance of the transient receptor potential, vanilloid 6 (TRPV6) Ca2+ channel in maternal,fetal Ca2+ transport was investigated using Trpv6 knockout mice. The Ca2+ concentration in fetal blood and amniotic fluid was significantly lower in Trpv6 knockout fetuses than in wildtypes. The transport activity of radioactive Ca2+ (45Ca) from mother to fetuses was 40% lower in Trpv6 knockout fetuses than in wildtypes. The ash weight was also lower in Trpv6 knockout fetuses compared with wildtype fetuses. TRPV6 mRNA and protein were mainly localized in intraplacental yolk sac and the visceral layer of extraplacental yolk sac, which are thought to be the places for maternal,fetal Ca2+ transport in mice. These expression sites were co-localized with calbindin D9K in the yolk sac. In wildtype mice, placental TRPV6 mRNA increased 14-fold during the last 4 days of gestation, which coincides with fetal bone mineralization. These results provide the first in vivo evidence that TRPV6 is involved in maternal,fetal Ca2+ transport. We propose that TRPV6 functions as a Ca2+ entry pathway, which is critical for fetal Ca2+ homeostasis. [source] Cytoplasmic calcium oscillations and store-operated calcium influxTHE JOURNAL OF PHYSIOLOGY, Issue 13 2008James W. Putney Intracellular calcium oscillations have fascinated scientists for decades. They provide an important cellular signal which, unlike most signalling mechanisms, is digitally encoded. While it is generally agreed that oscillations most frequently arise from cyclical release and re-uptake of intracellularly stored calcium, it is becoming increasingly clear that influx of calcium across the plasma membrane also plays a critical role in their maintenance and even in delivering their signal to the correct cellular locus. In this review we will discuss the role played by Ca2+ entry mechanisms in Ca2+ oscillations, and approaches to understanding the molecular nature of this Ca2+ entry pathway. [source] Characterization of Ca2+ signaling pathways in mouse adrenal medullary chromaffin cellsJOURNAL OF NEUROCHEMISTRY, Issue 5 2010Pei-Chun Wu J. Neurochem. (2010) 112, 1210,1222. Abstract In the present study, we characterized the Ca2+ responses and secretions induced by various secretagogues in mouse chromaffin cells. Activation of the acetylcholine receptor (AChR) by carbachol induced a transient intracellular Ca2+ concentration ([Ca2+]i) increase followed by two phases of [Ca2+]i decay and a burst of exocytic events. The contribution of the subtypes of AChRs to carbachol-induced responses was examined. Based on the results obtained by stimulating the cells with the nicotinic receptor (nAChR) agonist, 1,1-dimethyl-4-phenylpiperazinium iodide, high K+ and the effects of thapsigargin, it appears that activation of nAChRs induces an extracellular Ca2+ influx, which in turn activate Ca2+ -induced Ca2+ release via the ryanodine receptors. Muscarine, a muscarinic receptor (mAChRs) agonist, was found to induce [Ca2+]i oscillation and sustained catecholamine release, possibly by activation of both the receptor- and store-operated Ca2+ entry pathways. The RT-PCR results showed that mouse chromaffin cells are equipped with messages for multiple subtypes of AChRs, ryanodine receptors and all known components of the receptor- and store-operated Ca2+ entry. Furthermore, results obtained by directly monitoring endoplasmic reticulum (ER) and mitochondrial Ca2+ concentration and by disabling mitochondrial Ca2+ uptake suggest that the ER acts as a Ca2+ source, while the mitochondria acts as a Ca2+ sink. Our results show that both nAChRs and mAChRs contribute to the initial carbachol-induced [Ca2+]i increase which is further enhanced by the Ca2+ released from the ER mediated by Ca2+ -induced Ca2+ release and mAChR activation. This information on the Ca2+ signaling pathways should lay a good foundation for future studies using mouse chromaffin cells as a model system. [source] ,-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cellsJOURNAL OF NEUROCHEMISTRY, Issue 5 2009Nishani T. Hettiarachchi Abstract Parkinson's disease (PD) is characterized in part by the presence of ,-synuclein (,-syn) rich intracellular inclusions (Lewy bodies). Mutations and multiplication of the ,-synuclein gene (SNCA) are associated with familial PD. Since Ca2+ dyshomeostasis may play an important role in the pathogenesis of PD, we used fluorimetry in fura-2 loaded SH-SY5Y cells to monitor Ca2+ homeostasis in cells stably transfected with either wild-type ,-syn, the A53T mutant form, the S129D phosphomimetic mutant or with empty vector (which served as control). Voltage-gated Ca2+ influx evoked by exposure of cells to 50 mM K+ was enhanced in cells expressing all three forms of ,-syn, an effect which was due specifically to increased Ca2+ entry via L-type Ca2+ channels. Mobilization of Ca2+ by muscarine was not strikingly modified by any of the ,-syn forms, but they all reduced capacitative Ca2+ entry following store depletion caused either by muscarine or thapsigargin. Emptying of stores with cyclopiazonic acid caused similar rises of [Ca2+]i in all cells tested (with the exception of the S129D mutant), and mitochondrial Ca2+ content was unaffected by any form of ,-synuclein. However, only WT ,-syn transfected cells displayed significantly impaired viability. Our findings suggest that ,-syn regulates Ca2+ entry pathways and, consequently, that abnormal ,-syn levels may promote neuronal damage through dysregulation of Ca2+ homeostasis. [source] Prevention of a hypoxic Ca2+i response by SERCA inhibitors in cerebral arteriolesBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002C Guibert The aim of the study was to investigate the mechanism of a novel effect of hypoxia on intracellular Ca2+ signalling in rabbit cerebral arteriolar smooth muscle cells, an effect that was resistant to the L-type Ca2+ channel antagonist methoxyverapamil (D600). [Ca2+]i of smooth muscle cells in intact arteriolar fragments was measured using the Ca2+ -indicator dye fura-PE3. Hypoxia (PO2 10 , 20 mmHg) lowered basal [Ca2+]i but did not inhibit Ca2+ entry pathways measured by Mn2+ -quenching of fura-PE3. The effect of hypoxia was completely prevented by thapsigargin or cyclopiazonic acid, selective inhibitors of sarcoplasmic reticulum Ca2+ ATPase (SERCA). Since these inhibitors do not block Ca2+ extrusion or uptake via the plasma membrane, the data indicate that the effect of hypoxia depends on a functional sarcoplasmic reticulum. Because actions of nitric oxide (NO) on vascular smooth muscle are also prevented by SERCA inhibitors it was explored whether the effect of hypoxia occurred via modulation of endogenous NO release. Residual NOS-I and NOS-III were detected by immunostaining, and there were NO-dependent effects of NOS inhibitors on Ca2+i -signalling. Nevertheless, inhibition of endogenous NO production did not prevent the effect of hypoxia on [Ca2+]i. The experiments reveal a novel nitric oxide-independent effect of hypoxia that is prevented by SERCA inhibitors. British Journal of Pharmacology (2002) 135, 927,934; doi:10.1038/sj.bjp.0704547 [source] | |||||||||||||