Showing papers by "Parvinder K. Aley published in 2009"
TL;DR: This work shows that in both hippocampal neurons and glia, extracellular application of glutamate, in the absence of external Ca(2+), evoked cytosolic Ca( 2+) signals that were inhibited by preventing organelle acidification or following osmotic bursting of lysosomes.
Abstract: NAADP (nicotinic acid–adenine dinucleotide phosphate) is an unusual second messenger thought to mobilize acidic Ca 2+ stores, such as lysosomes or lysosome-like organelles, that are functionally coupled to the ER (endoplasmic reticulum). Although NAADP-sensitive Ca 2+ stores have been described in neurons, the physiological cues that recruit them are not known. Here we show that in both hippocampal neurons and glia, extracellular application of glutamate, in the absence of external Ca 2+ , evoked cytosolic Ca 2+ signals that were inhibited by preventing organelle acidification or following osmotic bursting of lysosomes. The sensitivity of both cell types to glutamate correlated well with lysosomal Ca 2+ content. However, interfering with acidic compartments was largely without effect on the Ca 2+ content of the ER or Ca 2+ signals in response to ATP. Glutamate but not ATP elevated cellular NAADP levels. Our results provide evidence for the agonist-specific recruitment of NAADP-sensitive Ca 2+ stores by glutamate. This links the actions of NAADP to a major neurotransmitter in the brain.
67 citations
TL;DR: Ned-20 prevents the self-desensitization response characteristic of NAADP in sea urchin eggs, confirming that this response is mediated by a high-affinity allosteric site to whichNAADP binds in the radioreceptor assay, and provides the first direct evidence for two binding sites (one high- and one low-Affinity) on the NAadP receptor.
42 citations
TL;DR: Ca2+ homeostasis in primary cultures of endothelial cells from human internal mammary artery and saphenous vein is compared and how this is modified by hypoxia, an inevitable consequence of bypass grafting is compared.
Abstract: Our understanding of vascular endothelial cell physiology is based on studies of endothelial cells cultured from various vascular beds of different species for varying periods of time. Systematic analysis of the properties of endothelial cells from different parts of the vasculature is lacking. Here, we compare Ca2+ homeostasis in primary cultures of endothelial cells from human internal mammary artery and saphenous vein and how this is modified by hypoxia, an inevitable consequence of bypass grafting (2.5% O2, 24 h). Basal [Ca2+]
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and store depletion-mediated Ca2+ entry were significantly different between the two cell types, yet agonist (ATP)–mediated mobilization from endoplasmic reticulum stores was similar. Hypoxia potentiated agonist-evoked responses in arterial, but not venous, cells but augmented store depletion-mediated Ca2+ entry only in venous cells. Clearly, Ca2+ signaling and its remodeling by hypoxia are strikingly different in arterial vs. venous endothelial cells. Our data have important implications for the interpretation of data obtained from endothelial cells of varying sources.
3 citations